Background: Interleukin-4 (IL-4) plays a central role in the humoral immune defense against nematode parasite infections, inducing IgE switch and regulation of worm expulsion from the intestines. The present study aimed to investigate the polymorphisms in IL-4 gene and their association with socio-demographic and environmental factors among patients with gastrointestinal complaints. Method: The screened population comprised 305 patients aged 3-50 years from Rawalpindi and Jhelum districts of Pakistan. A well-prepared questionnaire was administered to collect data on socio-demographic and environmental factors. The data were analyzed by using multiple logistic regression models. Molecular analysis was done on 88 confirmed cases passing worms and eggs in stool by using PCR to amplify IL-4 gene. Results: The result showed higher GI nematodes prevalence in Rawalpindi 34.87% and Jhelum 23.1% among gastrointestinal patients. The multivariate logistic regression model showed significantly (p<0.05) increased risk of infection in participants who were residing in rural areas (OR=321.94; 22.5), having poor economic status (OR=0.34), consuming raw/unwashed vegetables (OR=1.73; 15.39) and did not practice handwashing (OR=2.77; OR=0.30). Sequence analysis showed three novel polymorphisms at SNP g.704_705 ins T, g.3763_3764 ins AC and g.3792 G >A in patients with acute severe infections. Two known polymorphisms SNPs g.8455A>G and g.8492C>A were found in the intron region. Conclusion: IL-4 gene polymorphisms showed disease susceptibility and consuming raw/unwashed vegetables, poor handwashing practices and poor economic status were the most associated factors with the disease. Keywords: Interleukin-4; SNPs; Nematodes; Risk Factors; Pakistan.