BACKGROUND Myopia has been shown to be associated with many pathological complications including cataracts, and previous evidence supported that high myopia facilitates the formation of cataracts. However, no studies have identified a link between the genetic susceptibility of high myopia-induced cataracts (HMC) and the underlying genetic mechanisms. Our study aimed to determine how the TRIB2 and CAPRIN2 genes correlate to the risk of HMC. MATERIAL AND METHODS In total, we successfully recruited 3162 participants, including 1026 participants with high myopia and cataracts and 2136 controls with high myopia only. For genotyping, 22 tag single nucleotide polymorphisms (SNPs) in TRIB2 and CAPRIN2 genes were chosen. Single marker association analysis and functional effects of significant SNPs were carried out. RESULTS Strong correlation signals were captured for SNP rs890069 (χ²=22.13, P=2.55×10-6) in TRIB2 and SNP rs17739338 (χ²=16.07, P=6.10×10-5) in CAPRIN2. In patients with high myopia, the C allele at SNP rs890069 was strongly linked to cataract risk (OR [95% CI]=1.36 [1.20-1.55]). In patients with high myopia, the T allele at SNP rs17739338 was significantly related to a lower risk of cataract (OR [95% CI]=0.54 [0.40-0.74]). In different types of human tissues, SNPs rs890069 and rs17739338 were found to be significantly correlated to the levels of TRIB2 and CAPRIN2 gene expression. CONCLUSIONS Our study indicated that both TRIB2 and CAPRIN2 genes conferred the susceptibility to cataract in patients with high myopia and Chinese Han ancestry. Future research remains necessary for fully understanding the pathogenic mechanisms and genetic characteristics of cataract.