It is well known that [ 18 F]FDG PET has a low sensitivity in the detection of hepatocellular carcinoma (HCC). We prospectively compared [ 11 C]acetate PET/CT results with those of [ 18 F]FDG PET/CT in patients with HCCs.Thirteen patients (M:F=11:2, mean age of 51±12) with suspicious or confirmed HCCs underwent [ 11 C]acetate PET/CT with or without [ 18 F]FDG PET/CT (both [ 11 C]acetate and [ 18 F]FDG PET/CT were performed in 10 patients). HCC was confirmed by histopathology or clinical criteria in 12 patients and one benign liver lesion. Both PET/CT images were interpreted by two experienced nuclear physicians, supported by standardized uptake value (SUV).A total of 12 patients were confirmed to have initial or recurrent HCCs. [ 18 F]FDG PET/CT showed markedly increased uptake in only two patients, moderately increased uptake in another two and negative in six. [ 11 C]acetate PET/CT demonstrated markedly increased uptake in seven patients, moderately increased uptake in three and negative in only two. One HCC metastatic lesion was detected only by [ 11 C]acetate PET/CT. For detection of HCC, [ 11 C]acetate PET/CT showed a high sensitivity of 83%, whereas [ 18 F]FDG PET/CT only of 40%.The study results demonstrated that [ 18 F]FDG PET/CT has a limitation in detection of HCC and [ 11 C]acetate PET/CT has a complementary role to [ 18 F]FDG PET/CT. When primary HCC showed low [ 18 F]FDG uptake, it was [ 11 C]acetate-avid, and vice versa. It may be useful to combine both [ 18 F]FDG and [ 11 C]acetate PET/CT for detection of HCCs.