Background <p>Workers in the textile dyeing industry are occupationally exposed to high concentrations of particulates and volatile organic compounds (VOCs). This work aimed to study the environment-gene interaction as a risk factor for rheumatoid arthritis in textile dyeing workers.</p> Methods <p>This cross-sectional comparative study included 140 exposed male workers and 130 matched control workers. Air monitoring of chemical air pollutants in the workplace was conducted for 12 months. Estimation of anti-CCP, CRP, RF, ANA antibodies, and the <i>CYP2E1</i> and <i>GST</i> genes polymorphisms was studied in both groups.</p> Results <p>High air concentrations of PM₁₀, SO_2, H₂S, and VOCs were detected in the preparatory and dyeing sections compared to the printing section. Anti-CCP, CRP, RF, and ANA were statistically higher in exposed workers compared to the control group. Anti-CCP and RF in preparatory workers were significantly higher compared to printing workers. Multivariate analysis revealed interaction in <i>CYP2E1</i>,<i> GST</i> polymorphism and different environmental exposures on RF.</p> Conclusion <p>The environment-gene interaction of the elevation of PM10 and VOCs concentrations in the dyeing section, with the <i>CYP2E1</i> (<i>C2/C2</i> mutant genotype) and the <i>GST</i> (<i>M1</i> polymorphism), could be a risk factor for RF elevation in the workers from the dyeing section compared to the other two sections. The key recommendations include improving environmental control in the workplace, ensuring the proper use of personal protective equipment (PPE), conducting pre-employment screening for genetic susceptibility through genetic counseling for CYP2E1 and GST polymorphisms, and providing regular medical follow-up for workers carrying the CYP2E1 <i>(C2/C2)</i> genotype and the GST <i>(M1)</i> allele.</p>