Objective. To investigate the diagnostic value of magnetic resonance imaging (MRI) combined with serum alpha-fetoprotein (AFP), alpha-fetoprotein (AFP-L3), Golgi protein 73 (GP73), and des-γ-carboxyprothrombin (DCP) on early-stage primary liver cancer (PHC). Methods. A total of 122 patients who were treated in our hospital from January 2019 to May 2022 were included in this study, including 62 patients with early PHC (referred to as the observation group) and 60 patients with benign liver disease (referred to as the control group). MRI scans were performed on all participants, and MRI image features were compared. Subsequently, the differences in serum AFP, AFP-L3, GP73, and DCP concentrations of the two groups of patients were detected and compared. Receiver operating characteristic (ROC) curve was used to analyze the efficacy of MRI and each of the above tumor markers in diagnosing early PHC. Results. The proportion of low or slightly low signal on T1WI in the observation group was significantly greater than that in the control group, while the proportions of equisignal and high signal were lower than those in the control group. The proportion of high signal on T2WI and high signal on DWI in the observation group was higher than that in the control group, while the proportion of low or slightly low signal and equisignal was lower than that in the control group. Compared with the control group, the serum concentrations of AFP, AFP-L3, GP73, and DCP in the observation group were significantly increased (all
P
<
0.05
). For the diagnosis of early-stage PHC patients, MRI combined with these four markers showed favorable diagnostic value compared with parameter alone (area under the ROC curve, sensitivity, and specificity were 0.943, 0.919, and 0.833, respectively). Conclusion. MRI combined with serum AFP, AFP-L3, GP73, and DCP detection has good value in the diagnosis of early PHC patients, and can serve as an effective strategy to improve the early diagnosis rate of PHC.