The novel includes a brief prologue where the Jungle Hunter scans Earth from aboard its ship in orbit, surveying all of the species inhabiting the planet, finally studying an anatomical image of man.
The mission briefing takes place in the fictional country of Conta Mana, not Guatemala as in the film. Conversely, the mission itself takes place in Guatemala in the book, whereas the team enters the Republic of Val Verde in the film.
There are several differences with the characters in the book. Aside from the group generally being more bloodthirsty and savage, Mac is white, and both he and Blain are shown to be casually racist towards Dillon. Billy is actually psychic in the novel, able to access the memories of his ancestors and sense the Predator's presence, although he does not realise these abilities until after the assault on the guerrilla camp. While he certainly has something of a sixth sense in the film, it is never suggested that it is overtly supernatural.
Perhaps the most notable difference from the film is in the titular Predator itself. In the book, the Predator is a shapeshifter, capable of mimicking any creature it chooses after sampling it with just the slightest physical contact; at one point, it takes the form of a jackal after finding a tuft of the creature's hair wedged between some rocks. The Predator is even capable of dissipating entirely, vanishing and becoming part of the blowing breeze. In its basic form, it is a tall, humanoid creature with crimson, scaly skin and three-fingered hands. It's only weapons are a telescoping spear that it throws (incidentally similar to the Combi-Stick from Predator 2) and a static, spider web-like trap capable of contracting and shredding anything caught in it (similar to the net fired by the Net Launcher, again introduced in Predator 2). Instead of a Cloaking Device, the creature uses its shapeshifting ability and chameleon-like skin to hide. The Predator is also able to possess any animal it chooses (but not humans, one of the reasons it is so interested in them). It's blood is translucent and amber in color instead of green, although it still glows at night. The Predator does not kill men for sport, but rather out of scientific curiosity; the way it horrifically mutilates its prey is an attempt to study and better understand human beings. It does, however, keep trophies taken from those it kills on board its ship.
In the novel, the Predator first starts following the team after they discover the downed helicopter. In the film, the Predator doesn't pick up their trail until after they discover the skinned American Special Forces men.
The guerrilla camp is more substantial in the film, defended by anti-aircraft weapons and emplaced guns. It also sits atop an extensive underground bunker network, which is where all the weapons stockpiled for the invasion (briefly mentioned in the film) are stored.
Unlike in the film, following Hawkins' death, Dutch, Blain and Billy are immediately convinced they are being hunted by an alien. In the film, only Billy suspects they are being hunted by something that isn't human, and no one else is sure until much later.
Dutch and the team finds Hawkins' body hanging in the trees. In the movie, nobody notices it. Later, the Predator returns to its ship with Hawkins' body and tears out his spine and skull. In the film, it does this to Billy's corpse much later.
Before making his final stand, Billy applies American Indian-style warpaint to his face. In the film, his camo paint is inspired by Indian warpaint from the start. We find out how he dies, with the Predator slicing him open vertically from his neck to his stomach before tearing out his internal organs, presumably for study.
After going over the waterfalls, Dutch loses his clothes as well as his equipment, and consequently spends the entire final act of the story naked. Notably, after the Predator first fails to see him because he is covered in mud, Dutch actually watches the rescue helicopter fly overhead, but he is too weak to signal it. He subsequently passes out and has a vivid nightmare about being mutilated by the Predator.
During the final showdown, the Predator mimics Anna's voice to try and lure Dutch into a trap, almost succeeding before it gives itself away by also mimicking Mac, who is dead by this point.
The Predator actually flees when Dutch begins to gain the upper hand during the final fight, running back to its ship with Dutch in pursuit. At the ship, Dutch finds over thirty mutilated bodies and several flayed skins hanging from the surrounding trees, before finally killing the hunter with its own spear as it tries to board its ship, hurling the weapon straight through the Predator's head. The spear also damages something vital within the vessel, and it is the ship itself that then explodes, as the Predator does not have a Self-Destruct Device in the book.
When the chopper returns to find Dutch, the soldiers on board almost shoot him as they do not recognize him, but Anna stops them. The book notably ends with Dutch and Anna entering a relationship, something that is never mentioned in the movie.