Objective: To analyze the correlation between the levels of serum transcription activator factor 3 (ATF3), tumor necrosis factor receptor 1 (TNFR1), angiopoietin-like protein 4 (ANGPTL4) and the renal function, prognosis of patients with diabetic nephropathy. Methods: A total of 152 patients with diabetic nephropathy who were treated in the Second People's Hospital of Jiaozuo City from April 2022 to January 2024 were selected as the study group, and 152 patients with simple diabetes who were treated in the same period were selected as the control group. The levels of serum ATF3, TNFR1, ANGPTL4 and renal function indexes such as serum calcium, serum phosphorus, serum creatinine and glomerular filtration rate (eGFR) were compared between the two groups at admission, and their correlation was analyzed. The levels of serum ATF3, TNFR1 and ANGPTL4 in patients with different prognosis were compared at admission, and their correlation with prognosis and predictive value for prognosis were analyzed by partial regression. Results: Compared with the control group, the levels of ATF3, TNFR1, and ANGPTL4 in the study group were significantly higher at admission (P＜0.05). The levels of blood calcium and creatinine in the study group were higher than those in the control group, while the levels of blood phosphorus and eGFR were lower than those in the control group (P＜0.05). Serum ATF3, ANGPTL4, and TNFR1 were negatively correlated with blood phosphorus and eGFR, and positively correlated with blood calcium and creatinine levels (P＜0.05). In the study group, patients with poor prognosis had higher levels of ATF3, ANGPTL4, and TNFR1 on admission than patients with good prognosis (P＜0.05). Logistic regression analysis showed that serum ATF3, ANGPTL4 and TNFR1 were risk factors for poor prognosis of patients (P＜0.05). The efficacy of combined prediction of serum ATF3, TNFR1 and ANGPTL4 levels on admission in predicting poor prognosis of patients was 0.807, which was higher than that of each index alone (P＜0.05). Conclusion: The increase in serum levels of ATF3, TNFR1, and ANGPTL4 in patients with diabetic nephropathy is associated with their renal function. Clinical detection of these levels can help predict the prognosis of patients and provide effective reference for clinical diagnosis and treatment.