United States international Timothy Weah tore his hamstring again.
Former Paris-Saint Germain player Weah suffered the same injury in August, just few weeks after signing a five-year deal at Lille.
The 19-year-old - son of former Ballon d'Or winner George Weah - made only his third appearance for Lille as an 80th-minute substitute against Marseille in Ligue 1.
Weah played out the remainder of the 2-1 defeat. Later he confirmed on Instagram on Monday he had suffered a setback.
Lille then clarified the injury on Twitter as a right hamstring tear.
"Our forward will now begin a process of rehabilitation," the post read. "The entire team at LOSC wish Tim a speedy recovery."
Weah wrote on Instagram: "Felt amazing to be on the field again with my team-mates after six months, and thank you to our beautiful supporters who came out and cheered us on.
"But unfortunately for me, things didn't go as planned and I've injured myself again.
"Better days will come and I know that God is watching over me. Small setback for a major comeback."