To investigate the role of tumor necrosis factor α-induced protein 1 (TNFAIP1)-mediated RhoA ubiquitination in melanoma cell proliferation and invasion. Methods Bioinformatics analysis was performed to assess TNFAIP1 and RhoA expression in melanoma cell, followed by analyzing its expression in clinical tissues from melanoma patients. Gene and protein expression was assessed by RT-qPCR and Western blot assays, respectively. Human skin melanoma cell lines WM2664 and A2058 overexpressing TNFAIP1 and / or RhoA were established in vitro. Cell proliferation and invasion were investigated by colony formation, CCK-8 and Transwell assays. Plasmids expressing TNFAIP1 and RhoA were cotransfected into treated melanoma cells and immunoprecipitation assays were performed to determine the interaction between TNFAIP1 and RhoA. An in vivo model was established to confirm the effects of TNFAIP1 and RhoA on tumor growth and metastasis. Results Compared with adjacent normal tissues, TNFAIP1 expression was significantly decreased (P<0. 01) and RhoA expression was significantly increased (P<0. 01) in tumor tissues. Melanoma patients with high TNFAIP1 expression had a good prognosis, whereas melanoma patients with high RhoA expression had a poor prognosis. In vitro, TNFAIP1 overexpression significantly inhibited melanoma cell proliferation and invasion. TNFAIP1 mediated K48-linked ubiquitination of RhoA to promote its degradation. Rescue experiments showed that RhoA overexpression significantly inhibited the regulatory role of TNFAIP1 overexpression in melanin cell proliferation and invasion in vivo and in vitro. Conclusions TNFAIP1 has a tumor suppressor role in melanoma, which inhibits tumor cell proliferation and invasion by inducing RhoA ubiquitination.