Background: Roles of tobacco and alcohol use in etiology of cancer are well established. Alterationin in P53have essential roles neoplastic change by preventing genome mutation; the aim of this study was to assess theassociation between P53 mutation and tobacco and alcohol consumption, as well as to assess the epidemiology oftobacco and alcohol use as risk factors for cancer in the adult population of northern Saudi civilians. Materialsand Methods: A cross-sectional survey from October 2014 to January 2015, covering 3,398 adults, was performed.P53 mutation molecular detection was performed for 100 tobacco and alcohol users, usingDNA extracted frombuccal cells. Results: Of the 3,398 participants 3,253/3398(95.7%) responded, with a male female ratio of 1.10:1.00. Out of these, 24.8% had smoked tobacco in their lifetime and 2.7% were consumers of alcoholic beverages.None was identified with any P53 mutation. Conclusions: The prevalence of tobacco smoking among the northernSaudi civilians was relatively high. Females’ attitudes in tobacco and alcohol related issues were found to beaffected by social stigma. Tobacco and alcohol use has no link to P53 gene mutations.