C.J. Spiller tells TMZ Sports Jameis Winston "disrespected" Clemson University in a recent tweet ... and now, C.J.'s challenging his alma mater to DEFEND THE SCHOOL'S HONOR!
The tweet that C.J.'s referring to was posted over the weekend -- with the Florida State QB showing a pic of Clemson's football stadium along with the caption, "Our House."
FYI -- FSU kicked the crap out of Clemson when they played in the stadium back in October, winning 51-14.
"It's disrespectful," Spiller says ... "But it's all friendly. [Our] guys are gonna have to do something about it. We'll see come football season."
The Buffalo Bills running back also talked about the passing of team owner Ralph Wilson and how much he meant to the team.
BONUS UGLY FASHION MOMENT: Spiller's shoes. 'Nuff said.