Abstract: Objective To evaluate the alteration in morphous and function for A549 cells, which induced by antisense tankyrase oligomers (asTANKS) combinated with antisense human telomerase reverse transcriptase (ashTERT) oligomers and explore potential target of telomere-based molecular cancer therapeutics. Methods A549 cells was randomly assigned to 3 groups: ashTERT, ashTERT + asTANKS and asTANKS, while 3 groups (shTERT, sTANKS and blank) as control. With individual intervention for different hours, cells in morphous was observed by optical microscope, and proliferative activity evaluated by 3H-thymidine (3H-TdR) uptake assay and X-Gal transfection test as well. Moreover, apoptosis body was measured by Hoechst 33342 fluorescence staining, and besides, duration of proliferation by population double test analyzed. Results A549 cells was prone to senescence in morphous with asTANKS or ashTERT as passage time was delayed well and the trend combinated between asTANKS and ashTERT was more significant, in which apoptosis body appeared, Uptake rate in 3H-TdR trend to suppression and transfection efficiency in X-Gal was enhanced gradually under continuous treatment with ashTERT or asTANKS, but combinated effect was more markedly. Certainly, population double times was shortened more rapidly with the combination of asTANKS and ashTERT, although the same effect was observed with single factor. Conclusion In coordination with two telomere-based oligomers, A549 cells prone to come to the end more quickly, and it provides insight into strategies for telomere-based molecular cancer therapeutics.