Objective To observe the efficacy and adverse effects of conventionally fractionated (CF) versus hypofractionated (HF) three-dimensional conformal radiotherapy (3DCRT) for hepatocellular carcinoma (HCC) with portal vein tumor thrombosis.Methods A retrospective analysis was performed on the clinical data of 65 patients with HCC suitable for 3DCRT from 2008 to 2012.These patients were randomly divided into HF group (n =32) and CF group (n =32).The HF group received 3DCRT at a total dose of 45-55 Gy (3-4 Gy/fraction,3-5 fractions/week),while the CF group at a total dose of 40-56 Gy (2 Gy/fraction,5 fractions/week).Results The follow-up rate was 100％.For the HF group and CF group,the short-term response rates were 72％ vs.55％ (P =0.034),the 1-year local control rates were 72％ vs.55％ (P=0.034),the 1-year overall survival rates were 59％ vs.45％ (P=0.042),and the numbers of individuals with grade 1-2 acute gastrointestinal reactions,deterioration of liver function,and radiation hepatitis were 14 vs.11,8 vs.8,and 1 vs.0,respectively (P =0.237).Conclusions HF 3DCRT is superior to CF 3DCRT in the treatment of HCC.