Jia-Xia Li,1,* Chuan-Yuan Wei,2,* Shu-Gang Cao,1 Ming-Wu Xia1 1Department of Neurology, Hefei Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230000, People’s Republic of China; 2Department of Plastic Surgery, Fudan University, Shanghai 200032, People’s Republic of China *These authors contributed equally to this work Background: Nuclear auto-antigenic sperm protein (NASP) has been implicated in tumorigenesis. However, its role in melanoma is still unclear.Materials and methods: In the present study, we detected the mRNA and protein level of NASP in melanoma cell lines and tissues. Then the role of NASP was investigated by transfecting with NASP siRNAs. Finally, the prognosis of NASP was analyzed in 100 melanoma patients through Cox regression and Kaplan–Meier analyses.Results: We showed that NASP was significantly overexpressed in melanoma tissues, and unregulated NASP promoted melanoma cell proliferation via promoting cell cycle G1/S phase transition. Additionally, the expression of NASP was closely related to proliferating cell nuclear antigen, a widely accepted biomarker for cell proliferation. Clinically, we found that a high level of NASP predicated poor overall survival and high cumulative recurrence rates. Multivariate analysis revealed that NASP was a risk biomarker for predicting the prognosis of melanoma patients.Conclusion: Elevated NASP plays an important role in melanoma cell proliferation and tumor progression, and it can be used as an independent prognostic biomarker for melanoma patients. Keywords: NASP, melanoma, proliferation, prognosis