Background: The aim of our study was to identify the association between Human papillomavirus (HPV) positive rate and smoking in lung cancer (LC) patients. Meanwhile, to analyze differences among gender, age differences on HPV infection rate in LC patients. Methods: We performed a systematic literature search through PubMed, Wan Fang, China National Knowledge Infrastructure (CNKI), MEDLINE, EMBASE (OVID), and Web of Science databases from 1991-2017, and we searched these keywords such as "lung cancer", "HPV", "smoking", and "human papillomavirus". Review Manager 5.3 software was used to analyze. An estimate of the odds ratio (OR) with 95% confidence intervals (CI) was calculated. Results: In China, a statistical significance was observed between HPV positive rate and smoking in LC patients (OR=2.34, 95%CI: 1.76-3.09, P<0.001; I 2 =25%). However, after stratified by region, no significance was observed in other regions, gender, and age. Conclusion: HPV infections are associated with smoking in LC patients. The association between HPV infection and smoking in LC patients may relate to different regions. There were no differences between gender and age among HPV infection rates in LC patients. To identify the etiology of smoking, HPV, and LC, a further experimental research needs to be conducted.