This will be his first appearance since suffering a serious ear injury in a horror challenge by Millwall goalkeeper Liam Roberts at the start of the month.
Roberts received an extended six-match ban from the Football Association after being sent off for what could have been a career-ending challenge.
Mateta posted a video on Instagram after Sky Sports News reported he was fit to return, with an accompanying caption saying: "It's time."
He will don a special mask to protect his ear which could worsen if not covered up.
Speaking with Sky Sports last week, the 27-year-old said he is hopeful of a return which many Palace fans would welcome.
“Hopefully, I can play (against Fulham). Hopefully, you never know. Hopefully, they will see me. I’m in the ground every day. The doctor is the person, he will decide. I will wear a mask, I think so.”
The Frenchman will be a huge boost for manager Oliver Glasner whose FA Cup hopes could continue into the semi-final if his side manages to beat Fulham.
The next round could see them face the likes of Aston Villa, Manchester City, and Nottingham Forest in what is a great chance to pick up much-needed silverware for the Eagles.