Background: The study is the first of its kind to be conducted in Saudi Arabia (KSA), aiming to analyze the effectiveness of an intervention program in improving the knowledge of oral cancer among the youth. Materials and Methods: A total of 1,051 young Saudis (57% males and 43% females with a mean age of $20.4{pm}1.98$) were selected using multi-stage cluster sampling. Knowledge assessment was accomplished using a closed-ended questionnaire which was subjected to reliability tests. Prevalence of risk factors in relation to gender was analyzed using the chi-squared test. Effectiveness was calculated by comparing the pre- and post-intervention means, using the two-tailed paired t-test. Multiple logistic regression was employed in order to determine factors associated with awareness of risk habits, signs/symptoms and prevention of oral cancer. The significance level in this study was set at 0.05. Results: Females were seen to be more into the habit of sheesha smoking (3.3% rather than the use of other forms of risk factors. Prevalence of diverse risk factors such as cigarette smoking (20%), sheesha (15.3%), khat (27%) and shamma (9%) was seen among males. Gender and the use of modifiable risk factors among the study sample were significantly (p<0.001) associated with effectiveness of the intervention. The intervention program was highly effective (p<0.001) in improving the knowledge of oral cancer among the youth in Jazan, KSA. Multivariate analysis revealed that age and gender are the most significant factors affecting knowledge. Conclusions: The study gives a direction for further public health initiatives in this oral cancer prone region.