Helicobacter pylori is a gram-negative bacillus causing benign and malignant gastric diseases such as gastroesophageal reflux (GER). In larynx, H. pylori causes chronic inflammation and mucosal destruction that may lead to malignant changes. Although, H. pylori poses several virulence factors, cagA is probably the main factor in this regard. To evaluate the role of cagA gene in laryngeal squamous cell carcinoma (LSCC), a case-control study was conducted on patients with laryngeal complaints during 2010-2012. Seventy-two patients with LSCC (case group) and 72 patients without malignancy (control group) were included in the study. The H. pylori and cagA factor were assessed in laryngeal specimen of patients with PCR technique. 33 % of patients in case group (24 patients) and 45.8 % (33 patients) of control group were positive for H. pylori. CagA gene was present in 13.8 % (10 patients) of case group specimens and 31.9 % (23 patients) of control group. This difference was statistically significant with Mantel-Haenszel statistical test analyses. The results showed that patients with LSCC have significantly lower incidence of laryngeal H. pylori infection and cagA virulence factor than those without LSCC. Findings from this study support the protective effect of H. pylori infection against laryngeal cancer.