Objective: To explore the establishment of a subcutaneous transplanted tumor model of hepatocellular carcinoma in mice with Qi stagnation and blood stasis syndrome. Methods: Forty male C57BL/6 mice were randomly divided into 4 groups: NC group, QZXY group, Tumor group, and QZXY+Tumor group. They were categorized based on the modeling of Qi stagnation and blood stasis syndrome (7 days) combined with the modeling of subcutaneous transplantation tumor of hepatocellular carcinoma (20 days). Observations were conducted on syndrome manifestations, as well as tumor size and weight of the mice after modeling. Results: (1) Body weight: On the 7th day of modeling, the weight of QZXY group and QZXY+Tumor group was significantly lower than that of NC group (P<0.05). (2) Body temperature: On the 7th day of modeling, compared with NC group, the body temperature significantly decreased in QZXY group (P<0.05), while it increased in Tumor group (P<0.05). On the 27th day of modeling, the temperature of QZXY+Tumor group was significantly lower than that of NC group (P<0.05). (3) Syndrome manifestations: According to the syndrome scoring table, on the 7th day of modeling, mice in both QZXY group and QZXY+Tumor group exhibited Qi stagnation and blood stasis syndrome (P<0.05). As the modeling time extended, the score of mice in Tumor group increased with the formation of the tumor, the score of mice in QZXY+Tumor group was significantly higher than that of QZXY group (P<0.05). (4) Claw petechiae: Compared with NC group, the number of the claw petechiae was significantly increased in all three groups of modeled mice (P<0.05), with the QZXY+Tumor group showing the highest number. (5) Claw r value: Compared with NC group, the r value of the claw was significantly lower in all three groups of modeled mice (P<0.05). Additionally, the r value of the claw in the QZXY+Tumor group was consistently lower than that of the other three groups. (6) Open field activity: Compared with NC group, the vertical and horizontal activity of mice in QZXY+Tumor group decreased significantly (P<0.05). (7) Four coagulation indexes: Compared with NC group, APTT, TT and FIB were significantly increased in QZXY+Tumor group (P<0.05 or P<0.01). (8) Tumor size and weight: Compared with Tumor group, the tumor size and weight of QZXY+Tumor group increased significantly (P<0.05). Conclusion: This study successfully established a subcutaneous transplanted tumor model of hepatocellular carcinoma in mice with Qi stagnation and blood stasis syndrome. The findings indicate that Qi stagnation and blood stasis syndrome may occur during the course of liver cancer and could potentially further promote its development.