Objective In order to achieve better treatment effect, this paper evaluated the benefit-risk of imipenem combined with cefoperazone-sulbactam in the treatment of patients with severe infection based on multi-criteria decision making. Methods The clinical data of 96 patients with severe pulmonary infection admitted to our hospital from March 2020 to May 2022 were selected and divided into monotherapy group and combined treatment group according to different treatment methods, with 49 cases in each group. In the monotherapy group, cefoperazone-subactam was used alone, and the combined treatment group added the use of iminopenam on the basis of the treatment of the monotherapy group. Compared with the relevant indicators of the two groups, a multi-criteria decision-making model of imepepepepamine combined with cefoperazone-supadan was established for the treatment of patients with severe pulmonary infection, and the benefit value, risk value and the stability of the decision-making model of the two groups were evaluated. Results Compared with the control time of infection, drug treatment time, recovery time of lung function indicators and recurrence time of bacteriological examination in the combined treatment group, the monotherapy group were significantly shortened, and the total incidence of adverse reactions decreased significantly (P<0.05). The total efficiency and pathogen removal rate of the combined treatment group were significantly higher than that of the monotherapy group (P<0.05). There was no significant difference between the lung function index, blood routine index and inflammatory factor index of the two groups before treatment (P>0.05), but both groups improved significantly after treatment, and the improvement degree of CRP and PLT in the combined treatment group was significantly higher than that of the monotherapy group (P<0.05). The benefit value of the combined treatment group is 78, the risk value is 72, the total benefit-risk value is 75, while the monotherapy group is 60, 56 and 58 respectively. The benefit-risk of the combined treatment group is better than that of the monotherapy group with 100%, and the stability of the multi-criterion decision-making model is better. Conclusion For the treatment of patients with severe pulmonary infection, compared with the use of cefoperazone-supadan alone, combined with imidepenam is more effective, which can significantly improve the relevant indicators of lung function and inflammatory factors, as well as the occurrence of adverse reactions, providing a theoretical basis for clinical practice