Knowledge about oral cancer risk factors and signs is thought to improve prevention and early diagnosis, and in turn, increases survival. In this population-based survey, knowledge about oral cancer was assessed in Iran. A total of 1800 self-administered questionnaires (collecting sociodemographic data and questions regarding oral cancer risk factors and signs) were distributed through random sampling. Final scores ranged between 0 and 15 for the risk factors and 0–11 for the signs. Scores below the median indicated a low level of knowledge, scores representing the third quartile of correct answers indicated a moderate level of knowledge, and scores representing the upper quartile indicated a high level of knowledge. Statistical tests were used for analysis of knowledge level in different sociodemographic categories. A total of 1312 participants completed the questionnaires. The average of knowledge scores for risk factors was 5.3 ± 3.0 and for signs was 4.5 ± 2.9. Overall, 75 and 56% respectively were able to identify major risk factors (smoking and alcohol); 23.5% could not define any related signs and symptoms. Dividing scores into quartiles indicated that three out of four people had “low” knowledge about risk factors and 58% had “low” knowledge about signs and symptoms. Females and highly educated people had more knowledge of oral cancer. Significant difference was found between job and level of knowledge (P = 0.001). This survey revealed that public knowledge of oral cancer was not satisfactory in Iran. Efforts should be done to inform and educate people with risk factors, initial clinical presentation, and symptoms, in order to improve prevention and promote early diagnosis.