[Show abstract][Hide abstract] ABSTRACT: Malignant melanoma is an increasing disease in China, and its molecular mechanisms of development and progression are limited. The objective of this study was to investigate the expression of Ras interaction/interference 1 (RIN1) protein and its clinical significance in human melanoma. Immunohistochemistry was performed to detect the expression of RIN1 in 81 melanoma patients with a 5-year follow-up. The prognosis of the patients, classified by the clinicopathologic features and RIN1 expression, was assessed by multivariate analysis. RIN1 levels were then analyzed with overall survival (OS), progression-free survival (PFS), and recurrence-free survival (RFS) in the cohort. The biological function was determined by proliferation assay, flow cytometry analysis through knocking down of RIN1 in melanoma cells A375, as well as caspase-3 activation and PARP cleavage were detected by western blot or fluorometric assay. Data showed that RIN1 was overexpressed in melanoma samples. High-level RIN1 expression was observed in 49.4 % (40 of 81 cases), associated with thickness grade (P = 0.008) and lymph node metastasis (P < 0.001). Two distinguished subgroups were segregated by RIN1 levels within this set comparing prognostication of OS, PFS, and RFS. Importantly, RIN1 level was revealed as the significant independent prognostic factor for death and progression but a weak contribution for recurrence. Moreover, knock down of RIN1 expression in A375 cells, suppressed cell proliferation and induced apoptosis through caspase-3 activation and PARP cleavage. RIN1 expression could be a potential prognostic predictor for the melanoma patients and provide a potential target therapy for melanoma treatment.