Dyslipidemia is one of the known risk factors for cardiovascular disease, and its prevalence is increasing worldwide. At present, the study of dyslipidemia has gradually shifted from simple environmental or genetic factors to environment-gene interactions. In order to further explore the etiology and mechanism of dyslipidemia, we used occupational stress(OS) and LYPLAL1, APOC3 and SOD2 gene as research variables to explore their association with dyslipidemia.Here we used a case-control study to include Han workers from a coal mining enterprise in China to determine the association between study variables and dyslipidemia. Monofactor analysis showed that smoking, drinking, physical activity level, DASH diet score, sleep quality, BMI, hypertension, hyperuricemia, shift work, OS were significantly different between the two groups (P < 0.05). In the APOC3 rs2854116 dominant model, patients with CT/CC genotype had a higher risk of dyslipidemia than those with TT genotype. In SOD2 rs4880 recessive model, patients with GG genotype had a lower risk of dyslipidemia than those with AA/AG genotype, and the difference was statistically significant. We found that rs12137855 and OS, rs2854116 and OS, rs4880 and OS had joint effects, but no interaction based on the multiplication and addition model was found (Pinteraction > 0.05). GMDR model showed that the rs12137855-rs2854116-rs4880-OS four-factor model had the highest cross-validation consistency and training-validation accuracy (P < 0.05), suggesting that there was a high-order interaction between them associated with dyslipidemia. We found that dyslipidemia in coal miners was related to OS and genetic factors. Through this study, we revealed the dual regulation of environmental factors and genetic factors on dyslipidemia. At the same time, this study provides clues for understanding the etiology and mechanism of dyslipidemia.