Abstract: Objective To investigate the therapeutic effects and main side effects of highdose interferon alpha-2b（IFN-α-2b） adjuvant treatment in Chinese oral mucosal melanoma. Methods A total of 117 patients with oral mucosal melanomas with stage ⅢⅣA after surgery from May 2004 to November 2012 were analyzed retrospectively. In the 117 cases of oral mucosal melanoma， 73 cases received the adjuvant therapy of high-dose IFN-α-2b， of whom 58 cases finished the treatment（treatment group） and 15 cases discontinued treatment. The rest 44 cases who didn't receive high-dose IFN-α-2b adjuvant treatment were selected as the control group. The overall survival（OS）， relapsefree survival（RFS） and side effects between the two groups were compared. Results The median OS of 117cases was 40 months（95％CI：33-62months）. For the patients with stage Ⅲ， the differences of median OS（69 months vs.65 months） and RFS（50 months vs.34 months） were not significant between the two groups. While those of cases with stage ⅣA had significant differences， the median OS was 37 months vs. 20 months（P=0028）， and the RFS was 33 months vs. 10 months（P=0.004）. Furthermore， the benefit of treatment was greater for those of cervical lymph nodes involved in the patients with stage ⅣA. The median OS was 40 months vs. 20 months, the median RFS was 33 months vs. 10 months. Adverse reactions occurred in most patients treated with highdose IFN-α-2b. The common hematology toxicity was bone marrow suppression， including low counts of white blood cells and platelets. The other sideeffects included druginduced influenzalike syndrome， gastrointestinal responses and liver function damage. Toxicity of grade 1-2 was predominant， only 7 cases had grade 3-4 toxicity. After given symptomatic treatment， all of them could be relieved. No treatment-related death happened. Conclusion High-dose IFN-α-2b adjuvant treatment may improve overall survival time as well as relapse-free survival time in patients with advanced oral mucosal melanoma（stage ⅣA），and the side effects are tolerable.