: Cigarette smoking is a lifestyle behavior that causes significant adverse health effects. Cigarette smoke contains chemicals, many of which are lead to the production of reactive oxygen species (ROS), which can lead to apoptosis and autophagy. To estimate the association of Cigarette smoking with the autophagy and immunity, technology of real time polymerase chain reaction (RTPCR) for gene expression of (LC3A, LC3B, LC3C, myd88) was used. Enzyme-linked immunosorbent assay (ELISA) technique was utilized to measurement the amount of TNF-α protein. The ratios of LC3A/LC3B and LC3B/LC3C were calculated to estimate the autophagy flux. The results indicate the expression of LC3B, LC3C and Myd88 genes in smokers is increased significantly (p ≤ 0.001) compared with non-smokers. While the expression of LC3A gene is decreased significantly. Findings show that the serum mean concentration of (TNF-α) for smokers group is increased significantly (p ≤ 0.001). The ratio of LC3A/Lc3B is increased highly significant (p ≤0.001) in smokers individuals. While there is no significant differences in the ratio of LC3B/ LC3C between smokers and non-smokers.