Background: High dietary inflammatory index (DII®) scores, representing pro-inflammatory diets, have been associated with increased risks for numerous cancers. However, the evidence for renal cancer is limited. In the present study, we aimed to assess the association between DII and renal cancer risk in the Prostate, Lung, Colorectal, and Ovarian (PLCO) cohort. Methods: Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using a Cox proportional hazards model with adjustment for various potential confounders. Results: After a median 12.2 years of follow-up, this study recorded 443 renal cancer cases among 101 190 individuals. The DII score was positively associated with renal cancer risk in multivariable analyses. The HR in the highest DII tertile compared to the lowest tertile was 1.38 (95% CI 1.03-1.84). This was also true when DII was analyzed as a continuous variable. The HR of one-unit increment in DII for renal cancer risk was 1.07 (95% CI 1.01-1.12). Conclusion: In this large American cohort, pro-inflammatory diet, as estimated by higher DII scores, was significantly associated with a greater risk of renal cancer. Future large prospective studies are warranted to verify these preliminary findings.