Objective: To establish a mice model of liver cancer suitable for microwave ablation. Methods: C57BL/6J mice were randomly divided into 4 groups (n=10 in each group) and subcutaneously injected with Hepa1-6 cells of different numbers (5×105, 1×106, 2×106 and 5×106) respectively, and then the tumor formation rates in the 4 groups were compared. Next, the ideal cell number for tumor formation was selected to establish the mouse models once again. When mean tumor diameter reached 8–10 mm, the tumor-bearing mice were randomly divided into 4 groups (n=10 in each group) to undergo microwave thermal tumor ablation. The temperature at the edge of the tumor was maintained at 60, 55, 50, and 45℃ respectively, and the ablation time was 3 min. The complete ablation rate and pathological changes of tumor among the 4 groups were compared. Results: The group with 2×106 Hepa1-6 subcutaneous injection had a high tumor formation rate and was suitable for ablation. Except for 60℃ ablation group, in other 3 groups, the 55℃ ablation group had the highest complete ablation rate and the lowest recurrence compared with the other two groups (P<0.05). Conclusion: 55℃× 3 min microwave ablation is feasible and effective for Hepa1-6 cells subcutaneously implanted model of liver cancer in mice.