OBJECTIVE: The concept of "lifestyle" encompasses various factors, including nutrition, behavior, stress, physical activity, work habits, smoking, and alcohol consumption. Increasing evidence suggests that environmental and lifestyle factors can influence epigenetic mechanisms, such as DNA methylation, histone acetylation, and microRNA expression. Given that microRNAs (miRNAs) are an emerging focus in cancer research, there is growing interest in understanding how lifestyle choices affect miRNA responses. MiR-21 is well-established as an oncogenic miRNA, while miR-125a is reported as a tumor-suppressive miRNA in different cancers. This study aimed to analyze whether cigarette smoking and alcohol consumption are associated with altered levels of these salivary miRNAs in healthy individuals. METHODS: Saliva supernatant samples from 50 healthy individuals (10% smokers and 34% alcohol drinkers) were analyzed alongside non-smokers and non-alcohol drinkers using real-time polymerase chain reaction (PCR). The expression levels of miR-21 and miR-125a were compared across samples based on demographic characteristics, social status, and smoking and drinking habits. RESULT: The data showed overexpression of salivary miR-21 in individuals who regularly consumed alcohol and smoked, while miR-125a expression was not significantly affected in either group. CONCLUSION: The differential expression of salivary miR-21 in healthy individuals from a localized population suggests a correlation with common lifestyle risk factors.