Apolipoprotein C3 (APOC3) and angiopoietin-like protein 8 (ANGPTL8) genes are related to lipid metabolism. The relationships between single nucleotide polymorphisms (SNPs) in the APOC3 and ANGPTL8 genes with metabolic dysfunction-associated steatotic liver disease (MASLD) remain controversial. This study aimed to investigate the associations between specific SNPs in the APOC3 and ANGPTL8 genes and MASLD risk, with a particular focus on the mediating role of triglycerides (TG). A total of 440 participants were enrolled and categorised into MASLD and control groups. Genotyping of APOC3 SNPs (rs5128, rs2854116 and rs2854117) and ANGPTL8 SNP (rs2278426) was conducted using polymerase chain reaction-restriction fragment length polymorphism or Sanger sequencing methods. Multivariate logistic regression was employed to estimate the associations between these SNPs and MASLD risk, and mediation analysis was performed to assess the potential mediating effect of TG. We found that APOC3 SNPs were associated with MASLD risk, with increased odds ratios (ORs) indicating a higher risk of MASLD: rs5128 CG + GG genotype (OR = 1.8, 95% CI = 1.1-2.8), rs2854116 TC + CC genotype (OR = 1.9, 95% CI = 1.1-3.1) and rs2854117 CT + TT genotype (OR = 1.9, 95% CI = 1.2-3.2). No association was found between ANGPTL8 rs2278426 and MASLD (p > 0.05). Mediation analysis revealed that TG significantly mediated these relationships, accounting for 80.25% of the effect for rs5128, 64.61% for rs2854116 and 62.59% for rs2854117. In summary, polymorphisms in APOC3 (rs5128, rs2854116 and rs2854117) were associated with MASLD risk, with TG serving as a potential mediating factor. In contrast, ANGPTL8 rs2278426 polymorphism did not show any association with MASLD.