Smoking tobacco is probably the single most significant source of toxic chemical exposure to humans, and that affects many human organs .smoking is a major risk factor for various types of cancers.The specimenen compassed of two groups of volunteers: the group included 20 volunteers of smokers, the second group included14 volunteers of non-smokers as a control group. Surgical biopsy from oral buccal mucosa were taken and stained with ( P21,p27 clone) antibody by IHC, and we count the positive stained cells in two study groups to show if the gene p21,p27 is affected by cigarette smoking, and investigate the possibility of a mutation in it .statistical clear differences between the two groups . the control group is negative while the two groups was positive.