Objective The effect of hypoxia inducible factor-1α( HIF-1α) , p-glycoprotein ( p-gp) and human papillomavir-us(HPV) infection on non-small cell lung cancer (NSCLC) and their interrelationship are still not clear .The article aimed to study the relationship between HIF-1αand P-gp, their role in the occurrence , development and multidrug resistance of NSCLC , as well as the in-terrelationship among HIF-1α, p-gp expression and HPV infection . Methods By using immunohistochemistry , the expression of HIF-1αand p-gp was detected in 60 NSCLC tissues and 20 benign lung disease tissues .PCR was employed to detect the expression of HPV16/18 DNA. Results The positive expression rate of HIF-1αand p-gp was 48.3% and 60.0% respectively in NSCLC, but there was no positive expression of HIF-1αand p-gp detected in the benign lung disease group (P<0.05).The expression of HIF-1αwas in positive corelation with p-gp in NSCLC (r=0.313, P<0.05).The detective rate of HPV DNA was 41.7% in NSCLC group and 5.0%in the benign lung disease group , and there was a significant difference between them (P<0.05).The positive expression rate of HIF-1αin HPV DNA positive group and negative group was 52.0% and 45.7% respectively, which showed no significant difference (P>0.05).The positive expression rate of p-gp in HPV DNA positive group and negative group was 64.0% and 57.1%respectively, which showed no significant difference too (P>0.05). Conclusion HIF-1αand p-gp are involved in the occurrence, development and multidrug resistance of NSCLC .HPV infection may be one of the etiological factors in the carcinogenesis of NSCLC . However , neither the HIF-1αexpression nor the p-gp expression is associated with HPV infection .