Cigarette smoking is a harmful habit that is widespread around the world. It is among the well-known lifestyle-related risk factors for many diseases. Nicotine, as its principal constituent, has various detrimental, and beneficial functions. Nicotinic acetylcholine receptors (nAChRs), which are present in nearly all body cells, are how nicotine works. Numerous investigations have demonstrated that nicotine causes abnormal microRNA expression (miRNAs). These short sequences of RNAs are known to regulate gene expression post-transcriptionally. A wide range of miRNAs are modulated by nicotine, and nicotine-induced miRNA changes could subsequently mediate nicotine's effect on gene expression regulation. We will focus on the reciprocal interaction between nAChRs and miRNAs and describe the essential targets of these dysregulated miRNAs after nicotine exposure and activation of nAChRs. It appears that crucial subcellular mechanisms implicated in nicotine's effects are miRNA-related pathways. It is crucial to investigate the molecular mechanism underlying the effects of nicotine as well as the dysregulation of miRNA following nAChR activation. The finding about epigenetic mechanisms of nicotine-induced effects may shed light on the establishment of new treatment strategies to prevent the harmful effects of nicotine and perhaps may augment the beneficial effects in diverse smoking-related diseases.