Objective To explore the application effect of compound amino-polypeptide tablets combined with halometasonum cream in patients with psoriasis. Methods A total of 82 patients with psoriasis admitted to our hospital from May 2020 to January 2022 were selected as the research objects, and were divided into control group and observation group by random number table method, with 41 patients in each group. The control group was treated with halometasonum cream, and the observation group was treated with compound amino-polypeptide tablets (both groups were treated for 3 months, and the patients were followed up for 12 months). The symptom disappearance time, psoriasis area and severity index (PASI) score, inflammatory factors, adverse reactions and recurrence rate were compared between the two groups. Results After 3 months of treatment, the disappearance time of dark red skin lesions, skin itching, skin pain and skin hypertrophy in the observation group was shorter than that in the control group (P <0.05). The PASI score, IL-6, TNF-α, VEGF and CRP levels in the observation group were lower than those in the control group (P <0.05). There was no significant difference in the incidence of adverse reactions between the two groups (P >0.05). The recurrence rate of the observation group was 2.44% after 12 months of withdrawal, which was lower than 14.63% of the control group (P <0.05). Conclusion Compound aminopolypeptide tablets combined with halometasonum cream can shorten the disappearance time of symptoms in patients with psoriasis, reduce the levels of PASI and inflammatory factors, without increasing adverse reactions, and can reduce the longterm recurrence rate, which is worthy of clinical application.