AIM: To evaluate the association of complement factor H (CFH) and microtubule-associated protein 1 light chain 3 beta (MAP1LC3B) gene polymorphisms with the risk of age-related macular degeneration (AMD) in a high-altitude population. METHODS: The study group consisted of 172 participants with symptoms of AMD who were examined and diagnosed between January 2019 and June 2020. The control group was composed of 120 healthy individuals. Each participant was required to provide two milliliters of peripheral blood for DNA extraction. Two single nucleotide polymorphisms (SNPs) of CFH (rs1061170 and rs800292) and two SNPs of MAP1LC3B (rs8044820 and rs9903) were genotyped. The genotypes and allele frequencies of the SNPs in the study and control groups were further compared using Chi-square and Fisher’s exact tests. RESULTS: In a high-altitude population, the nominally significant differences of rs800292 and rs9903’s genotype AG frequencies were observed in the AMD group (P=0.034 and 0.004, respectively). The frequencies of allele G of rs800292 and allele A of rs9903 were also significantly different in the AMD group compared to the control [(P=0.034, OR=0.70, 95%CI: 0.50-0.98) and (P=0.004, OR=1.60, 95%CI: 1.15-2.22), respectively]. No significant differences in the genotype distributions (P=0.16 and 0.40, respectively) and allele frequencies (P>0.05) of rs1061170 and rs8044820 were observed in the AMD group. CONCLUSION: Genotype AG of rs800292 may be a protective factor for AMD. Conversely, rs9903 seems to be a risk factor for AMD. Therefore, allele G of rs800292 may be a protective factor, and allele A of rs9903, a risk factor for AMD in Qinghai high-altitude population.