Abstract: Death receptor pathway and perforin/granzyme pathway are the main mechanisms for immune system to kill tumor cells. SerpinB9 is the only known human protein that is able to inhibit the proteolytic activity of granzyme B (GrB). Expression of SerpinB9 has been observed in various human tumors, such as lung cancer and prostate cancer, and SerpinB9 can protect tumor cells from cytotoxic lymphocytes-mediated killing through the perforin/GrB pathway. In skin tumors, SerpinB9 expression has been detected in cells of malignant melanoma, cutaneous squamous cell carcinoma, cutaneous lymphomas, in which SerpinB9 contributes to tumor progression by mediating immune escape, resistance to immunotherapy and interference of the tumor microenvironment. In addition, researches have shown that inhibitor of SerpinB9 could retard the growth of melanoma, indicating the potential anti-tumor therapeutic application of SerpinB9 inhibition. The research status of SerpinB9 in skin tumors is reviewed in this paper.