Background Inter-individual differences in regulation and activity of xenobiotic metabolizing enzymes (XMEs) CYP1A and GST might cause distinct susceptibility to chronic rhinosinusitis (CRS) phenotypes that need to be explored. Therefore, the present study aimed to evaluate the role and risk of CYP1A and GST gene variants in allergic CRS subjects with and without asthma. A total of 224 allergic CRS cases with asthma, 252 allergic CRS cases without asthma, and 350 healthy control subjects were subjected to genetic analysis. Gene variants of cytochrome P450 (CYP1A1 T3801 rs4646903, A2455G rs1048943, C2453A rs1799814 and CYP1A2 G3858A rs2069514, T739G rs2069526, C163A rs762551) and glutathione S-transferase P (GSTP1 A313G rs1605 & C341T rs1799811) were investigated by polymerase chain reaction-restriction fragment length polymorphism and GSTM1null, and GSTT1null by multiplex PCR methods. Results TG genotype of CYP1A2 rs2069526 (OR 1.73, 95% CI 1.20–2.50, p < 0.002), TC genotype of CYP1A1 rs4646903 (OR 1.43, 95% CI 1.03–1.98, p < 0.031) and GSTM1del (OR 1.87, 95% CI 1.24–2.81, p < 0.003) and were found to be significantly associated with only allergic CRS cases. CYP1A2 rs2069526 (OR 2.33, 95% CI 1.61–3.37, p < 0.001), GG genotype of GSTP1 rs1605 (OR 4.75, 95% CI 2.62–8.63, p < 0.001), GSTM1del (OR 1.82, 95% CI 1.19–2.78, p < 0.006), GSTM1/GSTT1 double null (OR 2.58, 95% CI 1.36–4.87, p < 0.004) and were found to be significantly associated with asthma in allergic CRS cases. Further, G-G-C haplotype of CYP1A2 rs2069514, rs2069526 and rs762551 gene variants was found to increase the risk for asthma by 5 folds in allergic CRS subjects (OR 5.53, 95% CI 1.76–17.31, p < 0.003) while T-G-C haplotype of CYP1A1 rs4646903, rs1048943, rs1799814 (OR 0.11, 95% CI (0.01–0.95, p < 0.045) and A-T haplotype of GSTP1 rs1605, rs1799811 (OR 0.27, 95% CI (0.08–0.89, p < 0.032) showed protective effect in allergic CRS group. Conclusion The present study reports the significantly increased association of CYP1A2, GSTM, and GSTP gene variants with asthma in allergic CRS.