The ABO blood group has been recently proposed to influence development of oral cancer. The aim of this studywas 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 regardingthe patient demographics, blood groups, Rh status, cancer characteristics and oral habits were also comparedbetween 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 andoral 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. Accordingto Logistic Regression, people with blood group B and those older than 50 had 3.5 and 19.4 times elevated riskof developing oral cancer, respectively. The frequency of squamous cell cancer was also significantly higher inmen and people older than 50. On the other hand, females, people under 50, and those with blood group B wereat 5.6, 2.9 and 4.3 times higher risk of developing non-squamous cell oral cancer,respectively. People with bloodgroup B are at a greater risk of developing oral cancer, and female patients under 50 years of age with bloodgroup B have the highest risk to develop non-squamous cell oral cancer.