Objective The protein-energy wasting (PEW) often complicates with hemodialysis, resulting in a poorer life quality and a higher mortality in these patients. This clinical research studied the relationship between PEW and endogenous glucocorticoids (eGC) level and insulin resistance in maintenance hemodialysis patients (MHD). Methods A total of 70 MHD patients with malnutrition based on the modified quantitative subjective global assessment (MQSGA) score over 10 were selected, and 30 healthy adults were used as controls. We measured their biochemical parameters, body mass index (BMI) and anthropometry data. Fasting venous serum corticosterone before hemodialysis was measured by EIA. Fasting serum insulin was measured by ELISA, and insulin resistance was calculated by HOMA-IR. The correlation between nutritional parameters and corticosterone and HOMA-IR was analyzed. Results The MQSGA score of the 70 MHD patients was 12.97±2.36. Their body weight, BMI, triceps skinfold (TSF) and mid-arm circumference (MAC), as well as total serum protein and serum albumin, were all lower than those of the controls. Serum corticosterone was significantly increased compared with controls (10.82±14.52ng/L vs 2.35±3.68ng/L, P＜0.01). Fasting insulin significantly increased in MHD patients (25.2±9.9mmol/L vs 6.4±1.3mmol/L, P＜0.001), so did the HOMA-IR level (5.3±2.70 vs 1.39±0.49, P＜0.001). Spearman correlation analysis demonstrated that eGC was positively correlated to MQSGA (r=0.684, P＜0.001), and negatively correlated to MAC and mid-arm muscle circumference (MAMC). Fasting insulin and HOMA-IR levels were positively correlated to MAC, MAMC and serum triglycerides. Conclusions MHD patients with PEW are characterized by lower BMI, loss of muscle mass, but their serum albumin may still remain within normal range. The high levels of eGC and insulin resistance may relate to PEW status in MHD patients.