Objective To establish a mouse model of circulating tumor cells (CTCs) by applying mouse hepatoma Hapa 1-6 cells. Methods 108 healthy male C57BL/6 mice were randomly divided into 3 groups according to their body weights. Hepa 1-6 cell suspension was intravenously injected to each mouse in the three groups at a concentration of 1×10⁶, 5×10⁶ and 1×10⁷/mL, 0.2 mL per mouse, respectively. Blood samples were collected from the mice on the 1st, 5th, 9th, 13th, 17th and 21st days after tumor cell injection. The number, ratio and relative inhibition rate of CTCs were calculated in 20,000 nucleated cells. The mortality of mice was recorded. ②80 male C57BL/6 mice were averaged into 2 groups according to their body weight:control and sorafenib tosylate groups.0.2 mL of Hepa 1-6 single cell suspension was injected to each mouse through the caudal vein at a concentration of 5×10⁶/mL. The mice were gavaged with sorafenib tosylate (50 mg/kg) for 21 days and blood samples were collected at the 3rd, 8th, 15th, and 21st days for CTC assessment. Results For the 1×10⁶/mL group, the CTC inhibition rate was 25.1%, 18.1%, 8.9%, 4.4%, 2.9% and 0.3% on the 1st, 5th, 9th, 13th, 17th and 21st days, respectively, and all the mice were alive. For the 5×10⁶/mL group, the CTC inhibition rate was 40.4%, 35.4%, 15.4%, 9.0%, 6.6% and 4.1% on the 1st, 5th, 9th, 13th, 17th and 21st days, respectively, and all the mice were alive. For the 1×10⁷/mL group, the CTC inhibition rate was 39.1% and 33.5% on the 1st and 5th days, respectively. Some mice died immediately after intravenous injection and all mice died within 7 days. ②The relative clearance of CTCs was -7.5%, 4.6%, 55.3% and -94.5% on the 3rd, 8th, 15th and 21st days of sorafenib tosylate administration. Compared with the control group, there were significant differences among the three groups (P<0.05 or P<0.01). Conclusions A mouse model of circulating hepatoma cells has been established by intravenous injection of 0.2 mL of 5×10⁶/mL mouse Hepa 1-6 cell suspension. This mouse model can be used for screening and evaluation of drugs for circulating tumor cell inhibition.