Objective To investigate the influence of serum cystatin C (Cys-C) and hypersensitivity C-reactive protein (hs-CRP) levels on the 3-year survival of patients undergoing maintenance hemodialysis (MHD). Methods A total of 358 patients with chronic renal failure who underwent MHD at the Second Affiliated Hospital of Nantong University from April 2011 to October 2020 were selected as study subjects. General clinical data, pre-dialysis laboratory test indicators, and echocardiographic indicators 3 months after dialysis were recorded. The survival status of patients after 3 years of dialysis was followed up, and the general clinical data, pre-dialysis laboratory test indicators, and echocardiographic indicators 3 months after dialysis were compared between surviving and deceased patients. Univariate and multivariate Cox regression analyses were performed to screen influencing factors of 3-year survival in MHD patients. Results At the 3-year follow-up, of the 302 MHD patients' 203 survived, and 99 died. Statistically significant differences were observed in age, primary disease, diabetes status, congestive heart failure, statin use, antiplatelet drug use, diuretic use, dialysis mode, estimated glomerular filtration rate (eGFR) and gamma-glutamyl transferase (GGT), alkaline phosphatase (AKP), total bilirubin (TBIL), β₂-microglobulin (β₂-MG), creatinine (Cr), low-density lipoprotein cholesterol (LDL-C), hypersensitive C-reactive protein (hs-CRP), and serum phosphorus (P) levels between surviving patients and deaths(P < 0.05 or P < 0.01). Univariate Cox regression results showed that age of MHD patients, primary disease (diabetic nephropathy, hypertensive nephropathy, polycystic kidney disease, others), comorbidities(diabetes, congestive heart failure, other cardiovascular diseases), drug use (statins, antiplatelet drugs), dialysis method (hemodialysis, hemodialysis + perfusion), laboratory test indicators [GGT, AKP, TBIL, total bile acid (TBA), albumin (ALB), Cr, Cys-C, eGFR, apolipoprotein A (APO-A), hs-CRP]were all influential factors of 3-year survival rate of MHD patients. Multivariate Cox regression analysis revealed that age, primary disease, other cardiovascular diseases, dialysis mode, AKP, ALB, TBIL, Cys-C, and hs-CRP were significant influencing factors for the survival of patients with chronic renal failure (P < 0.05). Conclusion Serum Cys-C and hs-CRP levels before MHD in patients with chronic renal failure may be associated with their 3-year survival after dialysis treatment. High serum Cys-C may reduce the risk of poor clinical prognosis, while high serum hs-CRP may increase the risk of poor clinical prognosis.