This study aimed to explore the correlations of promoter methylation and single-nucleotide polymorphism (SNP) of brain-derived neurotrophic factor (BDNF) with post-traumatic stress disorder (PTSD) in Li and Han nationalities in Hainan province. Depression- and anxiety-related questionnaires were performed for PTSD-related information collection and analysis, with 164 PTSD patients and 141 healthy controls included. Serum BDNF level was measured and the methylation of BDNF promoter was evaluated. The BDNF SNP genotyping was performed, after which the risk genotypes for PTSD were detected and analyzed using logistic regression analysis. Our study found that the PTSD incidence was different in Li and Han nationalities. Serum BDNF level in PTSD patients in Li nationality was obviously lower than that in patients in Han nationality, while the methylation of BDNF promoter was higher in patients in Li nationality. The G-712A rather than rs6265 genotypes presented significant difference between PTSD patients and healthy controls. Meanwhile, the patients in Li nationality with AG genotype at G-712A inclined to depression, and patients with GG genotype had a greater degree of PTSD. G-712A and promoter methylation of BDNF were independent risk factors for PTSD. Our study demonstrated that the differences of PTSD patients between Li and Han nationalities were attributed by SNP G-712A genotypes and promoter methylation of BDNF.