This study examines the association between inflammatory biomarkers and risk of cancer mortality by race. Data were obtained from 1,856 participants in the prospective REGARDS cohort who were cancer-free at baseline, and analyzed in relation to cancer mortality prospectively. Biomarkers were log-transformed and categorized into tertiles due to non-normal distributions, and Cox proportional hazard regression models were utilized to compute hazard ratios with 95% confidence intervals using robust sandwich methods. Individuals in the highest tertile of IL-6 had over a 12-fold increased risk of cancer mortality (HR: 12.97, 95% CI: 3.46-48.63); those in the highest tertile of IL-8 had over a 2-fold increased risk of cancer mortality (HR: 2.21, 95% CI: 0.86- 5.71), while those in the highest tertile of IL-10 had over a 3-fold increased risk of cancer mortality (HR: 3.06, 95% CI: 1.35-6.89). In race-stratified analysis, each unit increase in IL-6 was associated with increased risk of cancer mortality among African- Americans (HR: 3.88, 95% CI: 1.17-12.88) and Whites (5.25, 95% CI: 1.24-22.31). If replicated in larger, racially diverse prospective cohorts, these results suggest that cancer patients may benefit from clinical or lifestyle approaches to regulate systemic inflammation as a cancer prevention strategy.