e21582 Background: Both chemotherapy and high-dose IFN-α2b (HDI) are effective treatment options in adjuvant setting for patients with resectable mucosal melanoma (MM). However, it is still unknown whether Ki67 level affects the selection of chemotherapy and HDI. Methods: Data from resected MM patients diagnosed as MM in Peking Cancer Hospital, were retrospectively collected and analyzed. Key inclusion criteria were: (1) diagnosed as resectable MM, with the date between Jan. 1, 2010, and Dec. 31, 2018; (2) Ki67 was identified by immunohistochemical staining; (3) received TMZ-based adjuvant chemotherapy or HDI. All patients were divided into two subgroups according to the Ki67 level proposed by previous publications: low (< 30%), high (> = 30%). Relapse-free survival (RFS) and melanoma-specific survival (MSS) were compared across different subgroups by log-rank tests. Multivariate Cox proportional hazards models were used to calculate hazard ratios (HRs), controlling for age, sex, primary site, lymphatic metastasis, LDH level, and gene mutational status (BRAF, c-KIT and NRAS). Results: In total, 1106 MM patients were screened and 175 met the inclusion criteria for analysis. 100 and 75 patients received temozolomide (TMZ)-based adjuvant chemotherapy and HDI therapy, respectively. Patients who received adjuvant chemotherapy had a superior RFS (21.0 vs. 9.6 months, HR = 0.47, P = 0.002) as compared to those with HDI, but no significant difference for MSS (45.9 vs. 37.6 months, HR = 0.63, P = 0.396). Longer RFS and MSS were observed in the ki67-low subgroup (HRs were 0.51, 95%CI 0.34-0.76 and 0.41, 95%CI 0.24-0.68 for RFS and MSS, respectively). For patients with low Ki67 (< 30%), two regimens showed no statistically different RFS (33.9 vs. 22.7 months, HR = 0.76, P = 0.329) and MSS (114.5 vs. 61.4 months, HR = 1.23, P = 0.967). However, for those with high Ki67, TMZ-based chemotherapy achieved an extended RFS compared with HDI (18.0 vs. 6.7 months, HR = 0.36, P < 0.001) and a trend toward improvement for MSS (41.4 vs. 25.1 months, HR = 0.47, P = 0.067). Conclusions: Ki67 level is an independent negative prognostic factor and impacts the selection of adjuvant treatment options for MM patients. Chemotherapy should be considered as the preference for patients with Ki67 > = 30%.