Oral cancer is a common site of head and neck cancer, and is relatively frequent in Northeast Thailand. The objective of this hospital-based, case-control study was to determine associations with risk factors. A total of 104 oral cancer cases diagnosed between July 2010 and April 2011 in 3 hospitals were matched with control subjects by age, sex and hospital. Data were collected by personal interview. There were significant associations between oral cancer and tobacco smoking (OR=4.47; 95%CI=2.00 to 9.99), alcohol use among women (OR=4.16; 95%CI=1.70 to 10.69), and betel chewing (OR=9.01; 95%CI=3.83 to 21.22), and all three showed dose-response effects. Smoking is rare among Thai women (none of the control women were smokers), but betel chewing, especially among older women, is relatively common. We did not find any association between practicing oral sex and oral cancer.