Background: Asians and Hispanics have the highest incidence rates of liver cancer in the United States, but little is known about how incidence patterns in these largely immigrant populations vary by nativity, acculturation, and socioeconomic status (SES). Such variations can identify high-priority subgroups for prevention and monitoring.Methods . Foreign-born Asian males and females had up to 5-fold higher rates than the U.S.-born. Among Hispanic females, incidence rates were elevated by 21% in higher-enclave versus lower-enclave neighborhoods, and by 24% in lower-versus higher-SES neighborhoods. Among Asian males, incidence rates were elevated by 23% in higher-enclave neighborhoods and by 21% in lower-SES neighborhoods. In both racial/ ethnic populations, males and females in higher-enclave, lower-SES neighborhoods had higher incidence rates.Conclusions: Nativity, residential enclave status, and neighborhood SES characterize Hispanics and Asians with significantly unequal incidence rates of liver cancer, implicating behavioral or environmental risk factors and revealing opportunities for prevention.Impact: Liver cancer control efforts should especially target foreign-born Asians, U.S.-born Hispanic men, and residents of lower-SES ethnic enclaves. Cancer Epidemiol Biomarkers Prev; 19(12); 3106-18. Ó2010 AACR.