Objective Investigating the key factors in constructing animal model of osteosarcoma. Methods 24 C3h mice (C3h/HeJ type 6, C3h/HeN type 18 at 4-8 weeks old) were randomly divided into 2 groups: A group: Subcutaneous inject 0.2 mL of 5×10⁷cells/ml mL LM8 suspension in lateral armpit before treated with depilatory creams; B group: subcutaneous inject 0.2 mL of 5×10⁷cells/mL LM8 suspension in lateral armpit before treated with shaver, and the tumor growth was recorded. Results The rate of A was 30% (4/12), and the rate of B was 100%. Conclusions Injected techniques and the way of post handle play important role in constructing osteosarcoma model.