【Objective】 To investigate the protective effect of the compound drug Weng-Li-Tong (WLT) against cisplatin (CDDP)-induced hepatocyte injury. 【Methods】 A cellular injury model was established by treating murine hepatocyte line BNL CL.2 with CDDP (80 μmol/L). Experimental groups were divided as follows: CDDP group (modeling only), WLT group (intervention with 1 g/L WLT), WLT+CDDP group (co-administration of CDDP and 1 g/L WLT), and a control group (normal culture). The protective effect of the compound drug WLT on CDDP-mediated hepatocyte injury was evaluated using CCK-8 assay, PI staining, crystal violet staining, Western blotting, reactive oxygen species (ROS) detection, and apoptosis analysis. 【Results】 Compared with the control group, the number of dead cells increased significantly (P<0.001) in the CDDP group, but no cytotoxicity was observed in the WLT group. The hepatocyte morphology in the WLT+CDDP group showed improvement with no obvious shrinkage compared to the CDDP group, as evidenced by the reduced proportion of PI-positive cells. Crystal violet staining results also indicated a higher cell count in the WLT+CDDP group than in the CDDP group, suggesting the protective effect of WLT against CDDP-mediated liver injury. Under CDDP intervention, the expression of the apoptosis-related protein Cleaved Caspase-3 increased. However, in the WLT+CDDP group, the expression of Cleaved Caspase-3 decreased, while the expression of the anti-apoptotic protein Bcl-2 increased. Additionally, compared to the CDDP group, the WLT+CDDP group showed a reduction in ROS production [DCFH-DA staining positive rate (%): 56.20±1.65 vs. 44.57±0.31] and a decrease in the proportion of apoptotic cells [proportion of early and late apoptotic cells (%): 43.60±0.44 vs. 19.57±0.78; 33.30±1.02 vs. 14.83±0.57] . 【Conclusion】 The compound drug WLT exhibits a protective effect against CDDP-mediated hepatocyte injury, suggesting potential therapeutic value in acute liver injury models.