Coffee consumption has been associated with the risk of cancer at several anatomical sites, but the findings, mostly from studies of non-Hispanic whites and Asians, are inconsistent. The association between coffee consumption and the incidence of cancer has not been thoroughly examined in African Americans. We conducted a nested case-control study including 1801 cancer cases and 3337 controls among African Americans from the Southern Community Cohort Study (SCCS) to examine the association between coffee drinking, as assessed by a semi-quantitative food frequency questionnaire, and the risk of four common cancers (lung, prostate, breast, colorectal). We used logistic regression adjusted for age, sex and cancer-specific risk factors. Overall, only ≤ 9.5% of African American cases and controls from the SCCS drank regular or decaffeinated coffee ≥ 2 times/day. After adjustment for major cancer-specific risk factors, coffee consumption was not statistically significantly associated with the risk of lung, breast, colorectal, or prostate cancers (OR range 0.78-1.10; P ≥ 0.27 for ≥ 2 versus < 1 times/day) or overall cancer risk (OR 0.93; 95% CI 0.75-1.16; P = 0.52 for ≥ 2 versus < 1 times/day). Coffee consumption was not associated with the risk of cancer among African Americans in our study.