Hidradenitis suppurativa (HS) is an inflammatory skin disease showing a chronic-remitting course. It has been rarely reported that long-term inflammation in HS could lead to serious complications like cutaneous squamous cell carcinoma. Cemiplimab is a fully human antibody immunotherapy that inhibits programmed cell death protein-1, approved for the treatment of locally advanced squamous cell carcinoma, or metastatic squamous cell carcinoma, in patients not eligible for curative surgery or radiotherapy. Herein, we report the case of a 56-year-old patient developing an invasive SCC on longstanding and unresponsive HS lesions successfully treated with cemiplimab.