Objective To establish a mouse model of cutaneous squamous cell carcinoma induced by 7,12-dimethylbenz(a)anthracene (7,12-DMBA)/croton oil and narrow-band ultraviolet B (NB-UVB) irradiation. Methods A total of fifty 6-8-week old BALB/c mice (male:female 1:1) were randomly divided into three experimental groups. The group A was treated with chemical carcinogens alone, group B was treated with NB-UVB alone, and group C was treated with chemical carcinogens plus NB-UVB. The general status and skin appearance of mice were observed during the experiment.The survival rate and tumor formation rate of each group was calculated at weeks 5, 10, 15, and 20. Pathological examination was carried out to observe the histological changes of skin lesions. Results Papules measuring ≥l mm in diameter began to develop in some mice of the group C at 5 weeks after the first treatment with chemical carcinogens. The tumor formation rates at 20 weeks after treatment were 86.67%, 7.14%, 94.12% in the groups A, B, C, respectively. Pathological examination revealed characteristic changes of squamous cell carcinoma in 13.34%, 0%, 70.59% of the mice in the group A, B, C, respectively. Conclusions Establishment of a mouse model of cutaneous squamous cell carcinoma induced by 7,12-DMBA/croton oil and NB-UVB is a better method than treated with chemical carcinogens alone or NB-UVB alone. This method can increase the tumor formation rate and incidence rate of SCC, and within a shorter period.