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Background: Alpha-fetoprotein (AFP) is one of the diagnostic standards for primary liver cancer (PLC); however, AFP exhibits insufficient sensitivity and specificity for diagnosing PLC., Aim: To evaluate the effects of high-risk factors and the diagnostic value of AFP in stratified PLC., Methods: In total, 289 PLC cases from 2013 to 2019 were selected for analysis. First, the contributions of high-risk factors in stratifying PLC were compared according to the following criteria: Child-Pugh score, clinical stage of liver cirrhosis, tumor size, and Barcelona Clinic Liver Cancer (BCLC) stage. Then, the diagnostic value of AFP was evaluated in different stratifications of PLC by receiver operating characteristic curves. For PLC cases in which AFP played little role, the diagnostic values of carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA 19-9), gamma-glutamyl transferase (GGT), and AFP were analyzed., Results: The roles of high-risk factors differed in stratified PLC. The incidence of smoking and drinking history was higher in PLC with Child-Pugh scores of C ( P < 0.0167). The hepatitis B virus (HBV) infection rate in PLC with cirrhosis was more than in PLC without cirrhosis ( P < 0.0167). Small tumors were more prone to cirrhosis than large tumors ( P < 0.005). BCLC stage D PLC was more likely to be associated with HBV infection and cirrhosis ( P < 0.0083). AFP levels were higher in PLC with cirrhosis, diffuse tumors, and BCLC stage D disease. In diagnosing PLC defined as Child-Pugh A, B, and C, massive hepatoma, diffuse hepatoma, BCLC stage B, C, and D, and AFP showed significant diagnostic value [all area under the curve (AUC) > 0.700]. However, these measures were meaningless (AUC < 0.600) in small hepatomas and BCLC A stage PLC, but could be replaced by the combined detection of CEA, CA 19-9, GGT, and AFP (AUC = 0.810 and 0.846, respectively)., Conclusion: Stratification of PLC was essential for precise diagnoses and benefited from evaluating AFP levels., Competing Interests: Conflict-of-interest statement: All the authors declare that they have no competing interests., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)