Through integrated analysis of GEO datasets and PI3K/AKT/mTOR pathway-related genes, we have systematically identified for the first time several key candidate genes—EIF4EBP1, GRSF1, IL11, HIF1A, and MMP3—several of which have not been systematically reported or validated in the context of cSCC. Here, MMP3 is linked to skin squamous cell carcinoma.