Objective To investigate the therapeutic efficiency and side effects of glucocorticoids combined with immunosuppressants for the cases of primary nephrotic syndrome with chronic renal failure in order to provide safe and efficient treatment in clinical practice. Methods A total of 50 patients with identified primary nephrotic syndrome with chronic renal failure in No.148 Hospital of Chinese PLA from December 2007 to June 2012 were enrolled in this retrospective study. All the patients were divided into 2 groups: the immunosuppressive treatment group and the conventional treatment group. The serum levels of albumin and cretinine, the 24-hour urine protein and the side effects were analyzed before and in 1, 3, 6, and 12 months after treatment respectively. Results In the patients of immunosuppressive treatment group, the level of 24-hour urine protein was significantly reduced in 1, 3, 6 and 12 months after the treatment. Meanwhile, the level of estimated glomerular filtration rate (eGFR) was increased significantly in 3, 6 and 12 months after the treatment. However, the level of 24-hour urine protein and the eGFR had no significant change in the conventional treatment group after 12 months treatment. There were differences in the side effects between the 2 groups, but without significant difference. Conclusion The combined treatment with glucocorticoids and immunosuppressants obviously reduces urinary protein, improves renal function, and?delays?the?development?of?renal failure in PNS patients with chronic renal failure.