Objective To investigate the significance of combined detection of alpha-fetoprotein-L3(AFP-L3) with glypican-3(GPC3) in diagnosis of primary hepatocellular carcinoma(PHC).Methods The 100 patients with PHC(PHC group),50 patients with cirrhosis(cirrhosis group) and 50 healthy subjects(control group) were enrolled in the study.The levels of AFP-L3 and GPC3 were detected by ELISA,and the levels of AFP were detected by radioimmunoassay,and the detection results were statistically analyzed.Results There were significant differences in the levels of GPC3 and AFP between PHC group and cirrhosis group(P0.01),so were between cirrhosis group and control group(P0.01).The positive rate of AFP-L3 in PHC group was significantly higher than that in cirrhosis group or control group(P0.01),and there was a significant difference between cirrhosis group and control group(P0.01).The positive rate of GPC3 in PHC group was significantly higher than that in cirrhosis group or control group(P0.01),however,there was no significant difference between cirrhosis group and control group(P0.05).In the combined detection of AFP-L3 with GPC3 for diagnosis of PCH,the sensitivity,specificity,accuracy were 97.0%(97/100),90.0%(90/100),93.5%(187/200),respectively,which was superior to that of any simple item detection.Conclusion The combined detection of AFP-L3 with GPC3 can enhance sensitivity,specificity and accuracy in diagnosis of PHC.