To explore the effect of calcipotriol betamethasone ointment combined with calcipotriol ointment in sequential treatment of psoriasis. Methods A total of 80 patients with psoriasis admitted to Rongcheng County People's Hospital from April 2022 to April 2023 were randomly divided into control group and study group, with 40 patients in each group. The control group was treated with calcipotriol ointment, and the study group was treated with calcipotriol betamethasone ointment combined with calcipotriol ointment sequential therapy. The clinical efficacy, skin lesion degree and adverse reactions were compared between the two groups. Results The total effective rate of the study group was 92.50%, which was higher than 72.50% of the control group (P <0.05). After treatment, the psoriasis area and severity index (PASI) score of the two groups was lower than that before treatment, and that in the study group was lower than that in the control group (P <0.05). The incidence of adverse reactions in the study group was 5.00%, which was lower than 25.00% in the control group (P <0.05). Conclusion During the treatment of patients with psoriasis, the sequential treatment of calcipotriol betamethasone ointment combined with calcipotriol ointment can reduce the degree of skin lesions, promote the improvement of clinical efficacy, and have high safety.