Abstract: Objective To investigate the safety and preliminary efficacy of apatinib combined with temozolomide in the treatment of advanced melanoma patients. Methods Nine patients with advanced melanoma after conventional treatment failures wereenrolled from December 2016 to May 2017.The patients were enrolled to three dose escalating groups（3 cases in each group）， with traditional 3+3 method， temozolomide100mg，apatinib 250 mg；temozolide 200 mg， apatinib 250 mg； temozolomide 200 mg，apatinib 500 mg， repeated every 28 days. Tumor response was evaluated by RECIST 1.1 criteria， and adverse events were graded according to NCI-CTCAE 4.0. The primary end point was safety （dose-limiting toxicity and maximum tolerated dose）， and the secondary endpoint was objective response. Results Dose escalation had been finished in nine patients without dose limiting toxicity （3 cases in each group）. Common adverse events included hypertension （33.3％）， hand foot syndrome （33.3％）， proteinuria（22.2％），white blood cell decrease （22.2％）， nausea（22.2％）， fatigue （11.1％）， etc. All adverse events were grade 1-2，maximum tolerated dose was not reached.Until May 2017， 7 patients could be evaluated， 1 got partial response（PR）， 4 got stable disease（SD） and 2 got progression disease（PD）， the objective response rate was 14.3％. Conclusion Apatinib combined with temozolomide is well tolerated withoutdose-limiting toxicity， and has shown its efficacy in advanced melanoma patients.