During end stage renal disease (ESRD) inflammatory pathways are activated which may lead to malnutrition inflammation syndrome (MIS). In the present study, 257 ESRD patients and 200 controls were included. Cytokine levels and genotyping was done by polymerase chain reaction-restriction fragment length polymorphism and enzyme-linked immunosorbent assay (ELISA). Risk was estimated through binary logistic regression. Cox proportional hazards regression and Kaplan-Meier were used for survival analysis. Tumor necrosis factor TNF-α-308 AA conferred 3.6-fold higher susceptibility (P=0.001) and higher TNF-α levels (P=0.05). TNF-α-238 AA was associated with 3.3-fold higher susceptibility to ESRD (P=0.002). IL-6-174 CC genotype conferred 3-fold risk to disease (P=0.001) along with higher IL-6 levels (P=0.001). IL-10-1082 GG genotype exhibited 2.2-fold higher susceptibility to disease (P=0.013). IL-10-592 AA/-819 TT genotypes were associated with high C reactive protein (P=0.02) and low IL-10 (P=0.03) levels. TNF-α-308 A allele was significantly associated with 2.3-fold higher risk of malnutrition. TNF-α-GAC, AGC and IL-6-CC were risk haplotypes associated with higher disease susceptibility. Combined analysis revealed 1.6-fold higher susceptibility to disease (P=0.02), there was 2-fold higher susceptibility to malnutrition (P=0.02) in high inflammation group. TNF-α-238 AA genotype was associated with 2.5-fold higher death hazard risk (P=0.02). Our study suggests that TNF-α and its genetic variants are major contributors to susceptibility to MIS in ESRD patients.