Objective To investigate the values of combined detection of C reactive protein (CRP), carcinoembryonic antigen (CEA) and α-L-fucosidase (AFU) in the early diagnosis of hepatocellular carcinoma (HCC). Methods From Mar. 2014 to Mar. 2017, the clinical data of 62 patients with early primary hepatocellular carcinoma (HCC group), 74 patients with liver cirrhosis (cirrhosis group) and 60 healthy subjects (control group) were retrospectively analyzed. The differences of serum CRP, CEA and AFU between the three groups were compared, and the difference of the diagnostic accuracy between the joint detection of three indicators, joint detection of two indicators and detection of single indicator was analyzed. Results The levels of CRP, CEA and AFU in the HCC group and cirrhosis group were significantly higher than those in the control group, and the levels of CRP, CEA and AFU in the HCC group was significantly higher than that in the cirrhosis group (P<0.05). The diagnostic accuracy of joint detection of CRP, CEA and AFU was 93.6% (58/62) which was significantly higher than that of single detection (P<0.05). Conclusion The combined detection of CRP, CEA and AFU which has positive significance for early diagnosis and early treatment, can effectively improve the accuracy of early diagnosis of hepatocellular carcinoma.