Objective: To explore the correlation between the levels of serum tumor necrosis factor receptor (TNFR) and the progression risk of diabetic nephropathy. Methods: Totally 195 patients with diabetic nephropathy, who were diagnosed and treated in our hospital from January 2017 to January 2018, were recruited. Patients were divided into progression group and non-progression group according to disease progression during follow-up. Biochemical indicators before treatment and TNFR levels before and after treatment were compared between the progression group and non-progression group. Cox regression was used to analyze the independent risk factors. Results: A total of 34 (17.43%) patients developed disease progression in this study. Significant differences in GFR, 24h urine protein > 1.5g, and parathyroid hormone were determined between the progression and non-progression groups (P < 0.05). Before treatment, the tertiles of TNFR1 were 2165 pg/mL and 2873 pg/mL, respectively, and the tertiles of TNFR2 were 5000 pg/mL and 12250 pg/mL, respectively there was a statistically significant difference in the number of patients with high and low TNFR1 and TNFR2 levels between the progression group and the non-progression group (P < 0.05). After treatment, no significant difference in TNFR1 and TNFR2 levels was found between the progression and non-progression groups (P > 0.05). Multivariate Cox regression analysis results demonstrated that high levels of TNFR1 (HR = 2.605, P = 0.031) and 24h urine protein > 1.5g (HR = 1.322, P = 0.004) were independent risk factors for disease progression. Conclusion: High levels of TNFR1 are significantly associated with progression and prognosis of renal disease in patients with diabetic nephropathy, and their levels are not affected by treatment.