The aqueous extract of C. sudachi peel suppresses serum- and EGF-induced cell proliferation and enhances differentiation induction in keratinocytes through inhibition of the EGFR–ERK signaling pathway; thus, it may be effectively used for the prevention and treatment of skin diseases, such as psoriasis and cutaneous squamous cell carcinoma, caused by abnormalities in proliferation and differentiation in epidermal keratinocytes. This evidence concerns the gene EGFR and cutaneous squamous cell carcinoma.