To investigate the association between single nucleotide polymorphisms (SNP) of IL-17A (rs2275913) and IL-17F (rs763780) genes and susceptibility to knee osteoarthritis (KOA) in Chinese Han and Tibetan populations. A case-control study was conducted. Total of 122 Han KOA patients and 124 Han healthy controls and 76 Tibetan KOA patients and 68 Tibetan healthy controls in Qinghai Province were selected between 2015 and 2017. SNP typing was performed on four groups of rs2275913 and rs763780 polymorphisms by polymerease chain reaction (PCR)-sequencing to detect IL-17A and IL-17 F genotype frequencies and allele frequencies. The test was used to compare data between groups. The genotype AA frequency of IL-17A (rs2275913) was significantly different between the Han KOA and the control group (2.625, 0.016). Compared with the frequency of allele A in healthy control group, the allele A frequency in Han KOA group was significantly higher(1.445, 0.047); the genotype frequency of IL-17A,however,was comparable between the KOA and the healthy control in Tibetan population (1.696, 1.355, both 0.05); there were also not difference in the IL-17F (rs763780) genotype frequency and allele frequency between the Han KOA and Tibetan KOA groups and two control groups,respectively (1.346, 1.126, both 0.05). It is highly likely that the pathogenesis of KOA in Chinese Han population is positively related to the genotype AA and allele A of IL-17A (rs2275913).