Background: Structural racism (SR) refers to interactive systems of discrimination that perpetuate advantage for one racial group over others. Single-variable SR measures, such as residential segregation and historical red-lining, are associated with cancer disparities but do not represent all aspects of SR. We aimed to develop a composite measure of SR for cancer research and examine the association of county-level SR with disparities in cancer mortality. Methods: Adapting methods from obesity and public safety research, we developed a SR composite score (SRCS) by calculating the ratio of Black to White performance on eight county-level variables across five domains (housing, education, employment, income and healthcare) using race-stratified census data from 2006-2020. Using North Carolina as a test set, we rank-ordered counties on a min-max scale 1-100 for each domain and averaged scores across domains to create the SRCS, where higher SRCS suggests greater SR. Outcomes were county age-standardized mortality rates (per 100k) for all cancers combined, breast, prostate, colorectal and lung cancers, extracted from CDC Wonder for non-Hispanic Blacks and Whites (2000-2020). We used generalized estimating equations to regress mortality rates on SRCS, race, and their interaction. Results: County-level SRCS was positively associated with county-level racial disparities in all-cancer mortality; for each 10-unit increase in SRCS, Black-White difference in rates increased by 15.3/100k (p<0.001). For individual cancers, a 10 unit rise in county SRCS was associated with a 1.93/100k increase in the colorectal cancer mortality gap (p=0.003) and a 6.18/100k increase in the lung cancer mortality gap (p<0.001). SRCS was not associated with mortality disparities for breast and prostate cancers, although these disparities were large. For all-cancer mortality and all tumor types except breast cancer, mortality rates of Whites significantly decreased as SRCS increased, while mortality rates for Blacks remained roughly stable with rising SRCS. Adjustment for county-level measures of social deprivation, unemployment, primary care provider ratio, and severe housing problems did not attenuate the relationship of SRCS with mortality. Conclusions: A composite measure of SR is associated with racial disparities in overall cancer mortality and mortality of specific solid tumors. Continued research is needed to further understand the role of area-level social determinants, ecologic fallacy, and differences in the relationship of SRCS to mortality across cancers. Nevertheless, increased SR is associated with lower county-level cancer mortality among Whites, suggesting that SR may perpetuate cancer mortality disparities via relative advantage to White residents rather than direct disadvantage to Black residents.