Objective To explore the biological function of PKP1 in skin cutaneous melanoma (SKCM). Methods The relative expression of PKP1 in different tumors and normal tissues was analyzed by real-time TIME 2.0 database. The expression of PKP1 in cutaneous melanoma tissues and normal tissues was analyzed by GEPIA and UALCAN databases, and the relationship between the expression level of PKP1 and the prognosis of tumor patients was explored. In SK-MEL-1 cell line, the effect of overexpression of PKP1 on tumor cells was explored. Results TIME 2.0 analysis showed that the expression level of PKP1 in various tumor tissues was lower than that in normal tissues (P<0.05), while the expression level of PKP1 in cholangiocarcinoma, liver cancer and renal clear cell carcinoma was higher than that in normal tissues (P<0.05). The GEPIA database showed that the expression level of PKP1 in normal tissues was higher than that in skin melanoma tissues (P<0.05). The protein level of PKP1 in PKP1 overexpression group was higher than that in NC group (P<0.05). The OS index of PKP1 high expression group was better than that of low expression group (P<0.05). CCK8 assay showed that the OD value of PKP1 overexpression group was statistically significant compared with that of empty plasmid group (P<0.01). Conclusion PKP1 is lowly expressed in cutaneous melanoma, and its down-regulation is related to poor prognosis. Meanwhile, PKP1 can inhibit the proliferation of cutaneous melanoma cells, and has the potential to become a key gene for targeted therapy