Inducted by Osmund Saddler into the Los Iluminados, Salazar contributed to the kidnapping of Ashley Graham using his castle as one of the Ganados' strongholds in Resident Evil 4.
Leon S. Kennedy and Ashley managed to get inside the castle after escaping from the infected villagers' forest. While inside the castle, Salazar managed to jack Leon's radio frequency in order to communicate with him throughout the game. Inside the castle, Salazar captures Ashley, forcing Leon to look for her once again.
In the boss battle, Salazar and one of his servants merged with the Las Plagas parasite, transforming into a plant-like mutant to battle Leon. Leon defeated Salazar, clearing the path to look for Ashley.