〔Abstract〕 Objective To investigate the therapeutic effect of pirfenidone combined with Nidanib on idiopathic pulmonary fibrosis. Methods A total of 100 patients with idiopathic pulmonary fibrosis admitted to Anyang People's Hospital from January 2019 to May 2022 were randomly divided into two groups with 50 cases in each group. The control group was treated with pirfenidone, and the observation group was treated with pirfenidone combined with nidanib. The total effective rate, incidence of adverse reactions, serum inflammatory factor index, vascular endothelial function index, pulmonary ventilation function index, pulmonary fibrosis score and quality of life score of the two groups were compared. Results The total effective rate of the observation group was higher than that of the control group, and the difference was statistically significant (P < 0.05). After treatment, the scores of serum inflammatory factors, vascular endothelin-1 and pulmonary fibrosis in the observation group were lower than those of the control group, and the scores of endodermal nitric oxide, forced expiratory volume in the first second (FEV1), FEV1/ vital capacity (FVC) and quality of life were higher in the observation group, the differences were statistically significant (P < 0.05). There was no significant difference in the incidence of adverse reactions between the two groups (P > 0.05). Conclusion Pirfenidone combined with nidanib has good efficacy in the treatment of idiopathic pulmonary fibrosis, which can reduce inflammatory response, pulmonary fibrosis degree and vascular endothelial injury in patients, improve lung ventilation function and improve quality of life in patients, and the drug safety is good.