Objective To investigate the predictive value of insulin resistance (IR) combined with neutrophil to lymphocyte ratio (NLR) on protein energy wasting (PEW) in male maintenance hemodialysis (MHD) patients with renal failure. Methods 145 male MHD patients with renal failure in the hospital were selected from February 2022 to February 2023. According to whether PEW occurred, they were divided into PEW group (41 cases) and non-PEW group (104 cases). The general data, homeostasis model assessment of insulin resistance (HOMA-IR) and NLR were compared between the two groups. Logistic multivariate regression analysis was used to analyze the risk factors affecting the occurrence of PEW. ROC curve was adopted to analyze the efficiency of HOMA-IR, NLR and combined detection on predicting the occurrence of PEW. Results Comparison of basic data in the two groups revealed that the age, proportion of diabetic nephropathy and dialysis time in the PEW group were older or higher than those in the non-PEW group (P<0.05). Compared with the non-PEW group, the HOMA-IR and NLR in the PEW group were higher (P<0.05). Logistic multivariate regression analysis showed that age, primary disease of diabetic nephropathy, dialysis time, HOMA-IR and NLR were independent risk factors for PEW occurrence (P<0.05). Spearman correlation analysis suggested that HOMA-IR and NLR were positively correlated with PEW (P<0.05). ROC curve analysis found that the areas under the curves of HOMA-IR, NLR and their combination in predicting PEW in male MHD patients with renal failure were 0.719, 0.714 and 0.742 respectively, and the area under the curve of their combination was the largest. Conclusion HOMA-IR combined with NLR detection has good predictive efficiency on predicting the occurrence of PEW in male MHD patients with renal failure