Objective To explore the relationship between HPV infection and polymorphisms of IL-1β and EGFR and lung cancer in non-smokers female. Methods A case-control study method was used, with 197 patients with lung cancer of non-smoking female lung cancer patients and 87 healthy female. The HPV DNA was detected with PCR technology, and the polymorphisms of IL-1β (-31C/T、-511T/C) and EGFR (-216G/T、-191C/A、8227G/A、D994D and R497K) were detected with TaqMan single nucleic acid polymorphism typing technology. Non-conditional Logistic regression was used to analyze the correlation between polymorphic genotype and lung cancer in non-smokers. Results The detection rate of HPV 16 in non-smoking female with lung cancer was significantly higher than that in the control group (P < 0.05). There was no significant difference in the gene polymorphisms of IL-1β-511 T/C and EGFR-191 C/A, -216 G/T, D99D, and R497K between the two groups (P > 0.05). There was statistically significant difference in IL-1β-31 C/T locus gene polymorphism between the two groups (P < 0.05), andthe risk of T/T genotype lung cancer was significantly increased (OR=0.25, 95% CI: 0.16～0.55). There was no statistically significant difference in the -191C/A, -216G/T, D99D and R497K gene polymorphisms of the EGFR gene between the two groups (P>0.05). there was statistically significant difference in EGFR-8227GA gene polymorphism between the two groups (P < 0.05), and the risk of G/A genotype lung cancer was significantly increased (OR=0.22, 95% CI: 0.18-0.57). Conclusions HPV 16 infection, IL-1β-31 T/T genotype, and EGFR -8227 G/A genotype are high risk factors for lung cancer in non-smoking female.