Objective: The main aim of this expreimental research study is to explore the impact of Betel Quid (BQ) on the Histopathological and morphometric alterations in the liver of adult mice (Swiss albino mice), focusing on discerning any significant differences in Histomorphometric effects between the application of Betel Quid with and without tobacco. Methods: This study was conducted as an controlled experimental animal investigation at the Department of Anatomy and Postgraduate Laboratory of Isra University over a period of six months, involving the selection of 30 adult mice (Swiss albino mice) of varying genders. Inclusion criteria for the sample population consisted of healthy male mice weighing between 25-40 grams and healthy female mice weighing between 20-40 grams, aged between 3-6 months. Exclusion criteria included unwell mice, offspring, moribund specimens, pregnant mice, underweight and malnourished mice. Following a 30-day period of administering appropriate nutrition to each mouse, euthanasia was performed via cervical dislocation. Subsequently, the livers were extracted, rinsed with normal saline, assessed for gross morphological parameters (such as weight and size) and any Histopathologic macroscopic abnormalities were documented (such as Infiltration, necrosis, fatty cahnges and more). The livers were then fixed in 10% formalin for a duration of 48 to 60 hours. Histological observations were conducted on 4-micron-thick liver sections stained with Haematoxylin and Eosin using standard paraffin embedding techniques. The animals were categorized into three main groups, each consisting of 10 mice: 1: Control group A (n = 10) received a standard diet and clean water, 2: Experimental group B (n = 10) received a standard diet supplemented with BQ containing tobacco, 3: Experimental group C (n = 10) received a standard diet supplemented with BQ without tobacco. Each of these groups was further divided into two subgroups of 5 male and 5 female mice each for more detailed analysis. Results: The result revealed significant Histopathologic and morphometric effects in the livers of adult mice when comparing the control group A with the experimental group B who chewied Betel Quid with tobacco, group C who chewied Betel Quid alone without adding of tobacco, Both experimental groups induced statistically significant hepatic alterations compared to the control group (Group A, p = 0.001). Both treated cohorts exhibited marked reductions in overall body weight and liver weight (Group B 1.18±0.13 g, Group C 1.33±0.04 g, while the Control group A 1.63±0.04 g, p = 0.001). Histopathological evaluation revealed extensive liver tissue damage across both experimental groups, characterized by significantly elevated rates of inflammatory infiltration, fatty changes, necrosis and collagen fiber fibrosis (p = 0.001 for all parameters versus control). Direct comparison between the exprimental Groups B and C showed that tobacco co-administration resulted in a significantly greater loss in liver weight (p = 0.004), a similar outcome was observed in the comparison between control and experimental group B (mostly with p-value 1.000). Furthermore, no significant discrepancy was identified when comparing Histopathologic and morphometric effects between group C and group B in both genders (p>0.05). In conclusion, it was determined that the consumption of BQ, with or without tobacco, induced similar significant effects on the livers of mice, notably affecting liver weight, degenerative alterations, fatty changes, necrotic manifestations, modifications in collagen fibers, liver infiltration changes and overall body weight. The comparative analysis between the two experimental groups led to the conclusion that the consumption of Betel Quid alone carries comparable risks to its consumption in conjunction with tobacco.