Objective To investigate the effects of a Chinese medicine Xiao Aiping injection on the pathological changes of liver tissues in rat models, the migration ability of cancer cells in hypoxic tumor microenvironment, and explore their mechanism of action. Methods Sixty SPF 5?week old male Sprague?Dawley rats were randomly divided into model group (n=48) and blank control group (n=12). The model group was intraperitoneally injected with diethylnitrosamine to establish hepatocellular carcinoma model, and the blank control group was injected equal amount of normal saline. After 14 weeks, the model group was equally divided into three groups, two of them received the Xiao Aiping injection at a low and high dose, respectively, and the rest of model group and the blank control group were injected with normal saline once per day for five days, lasting for consecutive four weeks. Liver specimens were collected at the nineteenth week, and the rat liver cancer and liver tissues were examined by pathology. In the hypoxic environment induced by CoCl₂ , the effect of Xiao Aiping injection on the migration ability of hepatocellular cancer SMMC?7721 and HepG2 cells was assessed by wound healing experiment, and the expression of IL?6 mRNA was detected by real?time PCR assay. Results Compared with the blank control group, hepatic tissue of the model group showed obvious hepatocellular carcinoma?like?changes indicating the successful establishment of hepatocellular carcinoma model. After treatment, compared with the model group, the pathological alterations of hepatic tissue of Xiao Aiping injection low and high doses groups were reduced, and were more obvious in the high dose group. Under hypoxic condition, Xiao Aiping injection obviously inhibited the migration of HepG2 cells and inhibited IL?6 expression in the liver tissues. With the same concentration, Xiao Aiping injection obviously inhibited the migration of SMMC?7721 cells, and showed an inhibiting trend of IL?6 mRNA expression, but the difference was not statistically significant. Conclusions Xiao Aiping injection can reduce the pathological changes of hepatocellular carcinoma in rat models induced by intermittent intraperitoneal injection of diethylnitresamine. In the chemically induced hypoxic environment, the effects of Xiao Aiping injection on the migration of SMMC?7721 and hepG2 cells are different. Downregulating the expression of IL?6 mRNA may be one of the mechanisms of migration inhibiting effects.