The river is implied by the documentary "A History of Liberty City" to be heavily polluted before even the establishment of the city itself, due to the natives using it effectively as a sewer.
- The Humboldt River is based on two different rivers in New York City and Northern New Jersey. Its real life counterpart is the East River, which separates Manhattan and Long Island. The name "Humboldt" and the river's status as the main river in Liberty City is based on the Hudson River, which actually separates New York and New Jersey. It is not influenced by the real Humboldt River that runs through northern Nevada.
- The game makes many references to murderers and serial killers hiding the bodies of people they have killed, or want to kill, in this certain river.
- Johnny Klebitz says the same thing in the mission Roman's Holiday, stating "I've seen some of the bodies you guys drop in the Humboldt" to the Russians.
- Because of the first meeting with Eddie Low, he may also use the Humboldt River to hide corpses.
- In Grand Theft Auto: Chinatown Wars, the protagonist, Huang Lee, is left for dead at the bottom of the river.
- A Tug Boat can be found under the Algonquin Bridge.
- The real Humboldt River runs through northern Nevada in the western United States.