|Spoiler Warning: Plot and/or ending details are in the text which follows.|
As with previous Grand Theft Auto games, safehouses are available for protagonists Michael De Santa, Franklin Clinton, and Trevor Philips, with six different safehouses available throughout the state of San Andreas. The protagonists can change clothes, watch TV, drink alcohol, or take drugs while in the safehouse. Additionally, certain safehouses have unique features: either Michael or Trevor can play tennis with Amanda at the De Santa house, and Franklin can interact with Chop at his safehouses. The player can store one or two vehicles in the garage, depending on its size. The player can still save the game at a safehouse by sleeping in the bed, advancing time by 6 in-game hours if playing as Michael or Franklin and 12 hours if playing as Trevor; however, saving game progress at the safehouse is a deprecated feature with the introduction of quick saving on the smartphone. While in the safehouse, the player cannot equip a weapon; however, if the player is wanted by the police, the player can use weapons to defend himself, but certain functions of the safehouse are disabled if a weapon is discharged.
|Strawberry Safehouse||Franklin||Forum Drive, Strawberry, Los Santos||Franklin and Lamar||Co-owned by Franklin and his aunt.|
Permanently unavailable after Hotel Assassination.
|De Santa House||Michael||Portola Drive, Rockford Hills, Los Santos||Complications||Temporarily unavailable between Caida Libre and Monkey Business.|
Permanently unavailable if the player assassinates Michael.
|Trevor Philips' Trailer||Trevor
|Zancudo Avenue, Sandy Shores, Blaine County||Mr. Philips||Only available to Michael between Caida Libre and Monkey Business.|
Permanently unavailable if the player assassinates Trevor.
|Debra's Apartment||Trevor||Goma Street, La Puerta, Los Santos||Friends Reunited||Permanently unavailable after Caida Libre.|
|Vanilla Unicorn||Trevor||Strawberry, Los Santos||Hang Ten||Permanently unavailable as a safehouse if the player assassinates Trevor.|
|3671 Whispymound Drive||Franklin||Whispymound Drive, Vinewood Hills, Los Santos||Hotel Assassination||Bought by Lester.|
- All three protagonists change safehouses at least once during the game; however, Trevor's Sandy Shores trailer is the only safehouse which remains available while Trevor remains a playable character.
- Franklin's Whispymound Drive safehouse can be accessed by any protagonist due to the patio windows in the kitchen and Franklin's bedroom being permanently open; however, neither Michael nor Trevor can use any the safehouse functions, and the safehouse is unavailable for Franklin until completing the Hotel Assassination mission.