The ABO blood group has been recently proposed to influence development of oral cancer. The aim of this study was to evaluate the association between the type of ABO blood group and oral cancer. In a case-control study, 104 patients with oral cancer were compared with 90 blood donors without cancer as controls. Data regarding the patient demographics, blood groups, Rh status, cancer characteristics and oral habits were also compared between two subgroups of squamous and non-squamous oral cancers. For statistical analysis, Chi-square test, t-student Test and Logistic Regression were used to analyze the relationship between ABO blood groups and oral cancer. The frequency of blood group B was significantly higher in oral cancer patients than controls (32% vs 13%) (p value=0.01), but Rh factor did not show significant difference between cases and controls. According to Logistic Regression, people with blood group B and those older than 50 had 3.5 and 19.4 times elevated risk of developing oral cancer, respectively. The frequency of squamous cell cancer was also significantly higher in men and people older than 50. On the other hand, females, people under 50, and those with blood group B were at 5.6, 2.9 and 4.3 times higher risk of developing non-squamous cell oral cancer,respectively. People with blood group B are at a greater risk of developing oral cancer, and female patients under 50 years of age with blood group B have the highest risk to develop non-squamous cell oral cancer.