Abstract. Microcephalin (MCPH1/BRIT1) is a large nuclear protein that is involved in the early cellular response to DNA damage, the expression of which is reduced in a variety of types of human tumors. A recent study by our group demonstrated that MCPH1 expression is markedly decreased in lung cancer. However, it remains unclear whether inducing the expression of MCPH1 may ameliorate lung cancer, and, if so, which mechanisms underlie this process. The results of the present study demonstrated that MCPH1 expression was downregulated in lung cancer tissues compared with that in normal lung tissues. Furthermore, MCPH1 overexpression in A549 non-small cell lung carcinoma cells, successfully inhibited cell proliferation via arrest of the cell cycle in the S and G2/M phases. In addition, MCPH1 overexpression promoted cell apoptosis, in association with a significant increase in the quantities of Bax and active caspase-3, as well as a decrease in the level of Bcl-2. In conclusion the present results indicated that MCPH1 is involved in the regulation of apoptosis and entry into mitosis, suggesting that MCPH1 may function as a tumor suppressor and that it may be important in the pathogenesis of lung cancer.