Objective To study the apoptosis pathway of human lung adenocarcinoma cell line A549 induced by 1-β-D-arabinofuranosylcytosine (Ara-C) in vitro. Methods A549 cells were incubated with Ara-C for 72hours in vitro. Biological changes of apoptotic cells were studied by TUNEL staining. Morphological changes of the A549 cells treated with Ara-C were observed by transmission electron microscope. The expressions of p53 and p73 were investigated by Western blotting. Results 1.Apoptotic rates of A549 cells exposure to Ara-C studied by TUNEL staining were higher than that of the control (P＜0.01). 2.Apoptosis body was apparently observed by transmission electron microscope. 3.Endogenous p73 but not p53 was induced and activated in dose-dependent manner upon Ara-C treatment by Western blotting.Conclusion Ara-C can effectively induce apoptosis of A549 cells. DNA damage-induced apoptosis of A549 cells treated by Ara-C is independent of functional p53.Up-regulation of p73 may play an important role that enhances the sensitivity of A549 cells to Ara-C and be partly responsible for p53-independent apoptosis.