Objective To analyze the role of photodynamic combined with cryotherapy in skin cancer. Methods A total of 90 patients with skin cancer admitted to our hospital from February 2020 to February 2022 were selected as the research objects. According to the random number table method, they were divided into control group (n =45) and observation group (n =45). The control group was treated with photodynamic therapy, and the observation group was combined with cryotherapy on the basis of the control group. The clinical efficacy, sleep quality, adverse reactions, appearance satisfaction and quality of life were compared between the two groups. Results The total effective rate of the observation group was higher than that of the control group (P<0.05). The PSQI and SIS scores of the two groups after treatment were lower than those of the same group before treatment, and those in the observation group were lower than those in the control group (P<0.05). The incidence of adverse reactions in the observation group was lower than that in the control group (P<0.05). The appearance satisfaction in the observation group was higher than that in the control group (P<0.05). After treatment, quality of life scores in the dimensions and total scores of the two groups were lower than before treatment, the observation group were lower than those in the control group (P<0.05). Conclusion Photodynamic therapy combined with cryotherapy is effective in the treatment of skin cancer, and no adverse reactions occur. Meanwhile, it can effectively improve the sleep quality and quality of life of patients, and the satisfaction is high.