Background. Tobacco smoking is frequently linked to the development of oral cancer and precancerous lesions. It causes alterations that can be seen histologically even in smokers' clinically normal oral mucosa. p16 is a critical protein involved in the activation of apoptotic pathways, which is frequently altered during carcinogenesis. The significance of angiogenesis in the growth of cancerous lesions has received a lot of attention. Changes in blood vessel size are a consequence of smoking. Using the endothelial cell marker CD34, researchers examined alterations in angiogenesis. Furthermore, as CD34 overexpression progresses from normal mucosa to dysplasia to carcinoma, it is thought to be a good marker for oral cancer progression. Objectives. This work aimed to investigate the smoking-induced histological changes in gingival tissue, aside from assessing the immunohistochemical expression of protein 16 and CD34. Material and methods. Gingival biopsies were obtained from healthy twelve middle-aged male patients during teeth extraction. The control group consisted of two nonsmokers, while the smokers' group consisted of ten patients. Histological and immunohistochemical examinations, as well as morphometric and statistical evaluations of p16 and CD34 expression, were performed on the samples. Results. In the current study, Smokers' gingiva showed some dysplastic alterations. Compared to the control group, the smokers' group exhibited significantly higher P16 immunoreactivity. However, there was a non-significant increase in CD34 immunoexpression. Conclusion. Our results concluded that although smoking is a known environmental risk factor for malignancy, smoking-induced oral epithelial dysplasia does not predict malignant transformation, since apoptosis and angiogenesis were not significantly affected.