Objective To investigate the dynamic changes in hepatocellular carcinoma-related indicators in the process of chemical induction of hepatocellular carcinoma in mice. Methods A total of 42 male C57BL/6J mice weighing 18 to 22 g were randomly divided into a treatment group and control group. Diethylnitrosamine combined with tetrachloride and olive oil was used to establish a mouse model of liver cancer. At weeks 4, 8, 12, 16, 20, 24, and 28 after treatment, the morphology, color, texture, and number of cancer nodules visible to the naked eye on the surface of the liver were evaluated in both the treatment group and control group. The liver and kidneys of the mice in each group were taken, the ratio of liver and kidney to body weight was determined, and hematoxylin-eosin staining was performed for pathological analysis. Changes of related blood indexes in the mice in each group were also determined. Results Compared with the control group, the body weight of the mice in the treatment group showed a trend of slow growth before 16 weeks and gradually decreased thereafter. Liver and spleen indexes were increased significantly with time. The serum levels of glutamic pyruvic transaminase, glutamic oxaloacetic transaminase, creatinine, and total bilirubin were increased significantly ( P <0. 05), while the serum levels of total protein, albumin, and urea nitrogen were decreased significantly ( P <0. 05). Pathological analysis also showed that as time progressed, the arrangement of hepatocytes in liver tissue gradually became irregular, and megakaryocytes and more obvious inflammatory cell infiltration were observed. Conclusions The success rate of a mouse hepatocellular carcinoma model induced by the optimized chemical method is high. Measurement of key indexes at 4, 8, 12, 16, 20, 24, and 28 weeks after treatment has practical significance for studying the dynamic changes of carcinogenesis and can reflect the development process of the relevant indicators of hepatocellular carcinoma in the model mice.