Objective: To investigate the likelihood of smoking and betel quid chewing behavior changes, as well as the associated factors, among subjects in a nationwide oral cancer screening program in Taiwan, where oral cancer is the fourth leading malignancy in men. Methods: The Taiwanese Oral Cancer Screening Program targets smokers and betel quid chewers over the age of 30. Between 2010 and 2021, 2,578,245 individuals participated in the program at least twice. During each visit, the central data monitoring center collected information on gender, age, education level, smoking and betel quid chewing habits, the quantities consumed, and diagnoses of oral potentially malignant disorders (OPMD) and oral cancer. A three-state Markov chain exponential regression model was employed to assess the probabilities of behavior change—deterioration, maintenance, or improvement—and the factors influencing these changes. Results: The largest proportion of both smokers and betel quid chewers remained unchanged in the repeated attendees. The smoking cessation transition result was less than 10%, whereas the reduction in dosage exceeded 20%. However, the discontinuation of betel quid chewing was observed in more than 20% of individuals in the low-dose group, and there was also a reduction in dosage of more than 20%. The positive OPMD caused the progression of Net Force Progression (NFP) from an initial stage of none, as well as NFP between low and high doses of both smoking and betel quid chewing. Higher levels of education, residing in urban areas, and receiving screenings in big hospitals help to avoid the progressive NFP between low and high doses of smoking. Additionally, these factors also help to prevent the development of NFP from an initial stage of none, as well as the progressive NFP between low and high doses of betel quid chewing. Conclusion: Participation in an Oral Cancer Screening program can effectively enhance hazardous oral behaviors including smoking and betel quid chewing. Although it may not have a substantial effect on smoking cessation, it can decrease the daily consumption of cigarettes. The approach demonstrates encouraging outcomes in encouraging individuals to quit betel quid chewing and decrease their daily consumption. Higher levels of education, urban residency, and receiving screenings at large hospitals all have a good impact on reducing dangerous oral cancer behaviors.