Macau is a former Portuguese colony. It has a population size of 680,000 with nearly 90% being ethnic Chinese. Cancer is the leading cause of mortality in the aging Macau population. Smaller population size, homogenous ethnic genetic background, and advanced economy make Macau an ideal place to practice populational cancer prevention. To know the basic information for the genetic background of cancer in the Macau population, we tested the germline variants in 68 major cancer predisposition genes from 5,062 Macau residents. We identified 6,441 genetic variants in the cohort, from which we identified 81 pathogenic variants with 122 carriers. Based on the data, we estimated the prevalence of 2.41% (1 in every 40 individuals) of cancer pathogenic variant carriers in the tested cohort, equivalent to 17,000 carriers in the entire Macau population of 680,000. The established database contains the detailed variant information, and provides a resource for comprehensive cancer control study in Macau and south Chinese populations.