To investigate the efficacy of calcipotriol cream combined with secukinumab in the treatment of patients with moderate to severe psoriasis. Methods From January 2021 to July 2023, 70 patients with moderate to severe psoriasis admitted to Qingjian County People's Hospital were selected and divided into control group and observation group by random number table method, with 35 patients in each group. The control group was treated with calcipotriol cream, and the observation group was treated with calcipotriol cream combined with secukinumab. The symptom scores and levels of inflammatory factors were compared between the two groups. Results After treatment, the observation group had lower scores of erythema and papules, skin itching, skin desquamation and skin lesions than those in the control group (P <0.05). The observation group had lower the levels of serum INF-γ, IL-2, IL-17 and TNF-α than those in the control group (P <0.05). Conclusion For patients with moderate to severe psoriasis, calcipotriol cream combined with secukinumab can effectively improve the clinical symptoms of and inhibit the level of inflammatory factors, which is worthy of clinical application.