Objective To analyze the clinical efficacy and safety of liquid nitrogen freezing combined with betamethasone injection in the treatment of keloid. Methods From April to October 2023, 150 patients with keloid admitted to Qingyang Hospital of Traditional Chinese Medicine were selected and randomly divided into control group and observation group, with 75 patients in each group. The control group was treated with betamethasone injection, and the observation group was treated with liquid nitrogen freezing on the basis of the control group. The clinical efficacy, recurrence, serum related factors, pain and itching symptoms, and quality of life were compared between the two groups. Results The total effective rate of treatment in the observation group was higher than that in the control group, and the recurrence rate was lower than that in the control group (P <0.05). After treatment, the level of TGF-β1 in the observation group was lower than that in the control group, and the levels of bFGF and BMP-7 were higher than those in the control group (P <0.05). After treatment, the scores of pain and pruritus in the observation group were lower than those in the control group (P <0.05). The scores of all dimensions of quality of life in the observation group were higher than those in the control group (P <0.05). Conclusion Liquid nitrogen freezing combined with betamethasone injection has a good clinical effect in the treatment of keloid diseases, which can relieve pain and skin itching symptoms by regulating serum related factors, so as to improve the quality of life and reduce the recurrence rate.