Abstract: Objective：To explore the safety and efficacy of the combination therapy of microwave ablation (MWA) and transcatheter arterial chemoembolization (TACE) in treating hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT). Methods：One hundred and fortyfive patients with HCC and Cheng’s classification Ⅰ (secondorder branch or segmental) PVTT were recruited. Seventyfive patients were treated with the combination of MWA and TACE. Seventy patients were treated with chemoembolization only. The overall survival (OS), response rate (RR), timetoprogression (TTP) and adverse events (AE) were compared. Results：In the combination therapy group, the survival rates at 12 and 24 months were 74.7 % and 51.7 %, respectively, and the median overall survival was 25.0 months (95%CI 19.6-30.4). In the control group, the survival rates at 12 and 24 months were 62.9 % and 29.1 %, respectively, and the median OS was 16.0 months (95%CI 11.3-20.7).Survival was significantly longer in the combination therapy group than in the control group(P=0.011). The median TTP was 22.7 months in the combination therapy group, and 12.4 months in the control group (P=0.006).The objective response rate was significantly higher in combination therapy group when compared with TACE only therapy group (combination therapy: 69.3 %, TACE only: 51.4 %; P=0.041). Conclusions：The combination of MWA and TACE is a safe and effective treatment modality in treating HCC and PVTT.