Abstract: Objective To investigate the association between single nucleotide polymorphism in the CYP1B1 rs1056836 and GSTP1 rs1695 and susceptibility of lung cancer in Xuzhou Han population. Methods From January 12,2017 to October 13,2017, a case-control study was performed for 100 lung cancer patients diagnosed by pathology and 100 healthy control individuals who were selected from center of Health Examination.The genetic polymorphisms of CYP1B1 rs1056836 and GSTP1 rs1695 were examined by real-time PCR. The association of these genetic polymorphisms and smoking and the combinations of these factors with the susceptibility of lung cancer was statistically evaluated. Results The individuals who carried with CYP1B1 rs1056836 and GSTP1 rs1695 mutant heterozygote and homozygote had a high risk of lung cancerOR=4.161,3.765和OR=2.904,3.037).Polymorphisms at two loci presented a joint effect(OR=11.667,95%CI=2.41-56.481,P<0.01).The combined CYP1B1 rs1056836 and GSTP1 rs1695 mutant genotype and smoking were found to be significant risk factros of lung cancer(OR=21.462,95%CI=4.643-99.2,P<0.01andOR=7.595,95%CI=2.769-20.835,P<0.01).Conclusion Genetic polymorphism of CYP1B1 rs1056836 and GSTP1 rs1695 is associated with risk of lung cancer among Xuzhou Han population.Both increase the lung cancer. These polymorphisms showed a synergy on the susceptibility to lung cancer ,presenting as higher risk with more risky factors included.Smoking showed a collaborative effect with two risky genetic factors