Abstract Background Diet, alcohol, cigarette smoking, physical inactivity, and body mass index have been studied as risk factors for renal cell cancer (RCC). The joint effects of these lifestyle factors, captured as Healthy Lifestyle Index (HLI), were examined in one previous study. This study aims to investigate the association between HLI score and RCC risk in the prospective Netherlands Cohort Study (NLCS). Methods A case-cohort analysis (3,767 subcohort members, 485 cases) was conducted using NLCS data ( n = 120,852). Data on aforementioned risk factors was used to calculate HLI score, ranging 0–20, with higher scores reflecting healthier lifestyles. RCC occurrence was obtained by record linkage to cancer registries. Multivariable-adjusted proportional hazard models were used to calculate Hazard Ratios (HR) and 95% Confidence Intervals (95%CI). Results Compared to participants in the unhealthiest HLI category, participants within the healthiest category had a lower RCC risk (HR = 0.79, 95%CI = 0.56–1.10, p for trend 0.045). A standard deviation (± 3-unit) increase in HLI score was not statistically significantly associated with a lower RCC risk (HR = 0.92, 95%CI = 0.83–1.01). This association was stronger after excluding diet or alcohol from the score, although confidence intervals overlap. Conclusions Adherence to a healthy lifestyle was weakly, though not statistically significantly, associated with a lower RCC risk.