Abstract There is currently no data about the genetic variations of APOE in Hakka population in China. The aim of this study was to analyze the allelic and genotypic frequencies of APOE gene polymorphisms in a large ethnic Hakka population in southern China. The APOE genes of 6,907 subjects were genotyped by the gene chip platform. The allele and genotype frequencies were analyzed. Results showed that the ∊3 allele had the greatest frequency (0.804) followed by ∊2 (0.102), and ∊4 (0.094), while genotype ∊3/∊3 accounted for 65.43% followed by ∊2/∊3 (15.85%), ∊3/∊4 (14.13%), ∊2/∊4 (3.01%), ∊4/∊4 (0.84%), and ∊2/∊2 (0.74%) in all subjects. The frequencies of the ∊4 allele in Chinese populations were lower than Mongolian and Javanese, while the frequencies of the ∊2 allele were higher and ∊4 allele lower than Japanese, Koreans, and Iranian compared with the geographically neighboring countries. The frequencies of ∊2 and ∊4 alleles in Hakka population were similar to the Vietnamese, Chinese-Shanghai, Chinese-Kunming Han and Chinese-Northeast, and French. The frequency of ∊2 in Hakka population was higher than Chinese-Dehong Dai and Chinese-Jinangsu Han. The low frequency of the APOE ∊4 allele may suggest a low genetic risk of Hakka population for cardiovascular disease, Alzheimer’s disease, and other diseases.