Ruiz was carried off the pitch towards the end of Fulham's 1-1 draw with West Brom at Craven Cottage on Saturday, and he could now be set for a period on the sidelines.
The Costa Rica international's pain seemed to be the result of a heavy tackle from West Brom defender Liam Ridgwell, and boss Martin Jol confirmed that the player will now face tests to determine how serious the issue is.
He said: "(Bryan) Ruiz's (injury) looks quite serious so we have to scan him and wait and see what the problem is.
"It is with his ankle. I have no idea of the severity of it but we will see."
The news comes as a blow to Fulham, who could also now be without Dimitar Berbatov after the forward asked to be withdrawn against West Brom due to a hamstring strain, although former Tottenham manager Jol is hopeful that the Bulgarian's injury is not a major one.
"Berbatov had a hamstring (problem)," he added. "I don't think that is serious. He gave us signal that he wanted to be substituted and hopefully it was just in time."
