Objective To analyze the clinical characteristics and risk factors of thyroid dysfunction caused by programmed cell death protein 1 (PD-1)/programmed cell death protein ligand 1 (PD-L1) inhibitor in patients with malignant tumors. Methods The clinical data of 109 patients with malignant tumors from March 2022 to March 2024 were retrospectively analyzed. All patients were treated with PD-1/PD-L1 inhibitors. The differences in gender, age, history of surgery, chemotherapy history, radiotherapy history and thyroid nodules were compared between patients with thyroid dysfunction and patients with normal thyroid function after PD-1/PD-L1 inhibitor treatment, and the risk factors of thyroid dysfunction were analyzed. Results 109 patients met the inclusion criteria, including 39 cases (35.78%) with thyroid dysfunction. Univariate analysis showed that there were statistical differences in gender ratio, BMI ratio, disease course, targeted drug therapy history and thyroid peroxidase antibody (TPO-Ab) expression (P＜0.05). The proportions of female, BMI＞23.90 kg/m2, disease course＞1 year, history of targeted drug therapy and positive TPO-Ab in thyroid dysfunction group were significantly higher than those in normal thyroid function group (P＜0.05). Multivariate analysis showed that female, BMI＞23.90 kg/m2, course of disease more than 1 year, history of targeted drug treatment, and positive expression of TPO-Ab were independent risk factors for thyroid dysfunction (P＜0.05). Conclusion The risk of thyroid dysfunction in patients with malignant tumors is high after PD-1/PD-L1 inhibitor treatment. Gender, BMI, disease course, history of targeted drug therapy, and TPO-Ab expression are the influencing factors of thyroid dysfunction after PD-1/PD-L1 inhibitor treatment. Therefore, it is necessary to take early intervention for patients with the above factors in clinical treatment to avoid thyroid dysfunction after PD-1/PD-L1 inhibitor treatment