Introduction: One of the risk factors for cancer is the habit of smoking. Some carcinogenic substances in ciga-rettes are nicotine and nitrosamine. In cigarette smoke there are free radical molecules or Reactive Oxygen Species (ROS) that can cause DNA mutations that can disrupt the balance of cell metabolism. One of them is the apoptosis, apoptosis is a programmed cell death mechanism. In cancer conditions there are apoptotic disorders and excessive proliferation of cells. The process of apoptosis is influenced by the death receptor, Tumor Necrosis Factor apoptosis inducing ligand R1 (TRAIL R1). This study aims to determine the effect of smoke exposure to expression of TRAIL R1 on the mucosal epithelium of the tongue of the Wistar rat (Rattus Novergicus). Methods: The subjects of this study were 24 male Rattus Novergicus with the age range of 12-14 weeks and weighing ± 170 grams. Divided into 4 groups with 2 control groups 4 weeks (K4), 8 weeks (K8) and 2 treatment groups each given 2 cigarettes / day ex-posure to cigarette smoke for each rat for 4 weeks (P4) and 8 weeks (P8). Results: The results showed that exposure to cigarette smoke can cause interference with TRAIL R1 expression. There was a significant difference in TRAIL R1 expression between the control and treatment groups and there was a significant difference in TRAIL R1 expression between the duration of cigarette smoke exposure (P4 and P8). Conclusion: Exposure to cigarette smoke can interfere with the process of apoptosis.