The aim is to investigate the adaptive response in radiation-induced bystander H1299 non-small cell lung cancer cells and the potential roles TGF-β 1 pathway plays in the response. Medium transfer method was used to obtain radiation-induced bystander cells; clonogenic assay was used to observe the adaptive response in bystander cells after irradiation; Western Blotting was used to detect the alteration of SOD2 expression in bystander cells. The data show that the conditioned medium collected from both unirradiated and irradiated cells did not cause any change in the clonogenic cell survival of bystander cells. However, when bystander cells were irradiated with 2 Gy of X-rays after being cultured in 1 h or 18 h non-radiation conditioned medium, its clonogenic cell survival was 12% or 38% greater than that cultured in fresh medium. The clonogenic cell survival of cells irradiated with 2 Gy of X-rays after culture in 1 h or 18 h radiation conditioned medium was 10% greater than that cultured in relative non-radiation conditioned medium. Furthermore, when the signaling cells were pretreated with a TGF- βR1 inhibitor, SB431542, the adaptive response in bystander cells no longer occurred. But adding SB431542 into the conditioned medium caused more complex consequence. On one hand, it did not affect the adaptive response in bystander cells cultured in the conditioned medium harvested 1 h post irradiation; on the other hand, while it decreased the adaptive response in bystander cells cultured in the non-radiation or radiation conditioned medium harvested 18 h post irradiation by 28% or 18% compared with that without SB431542, it increased the difference of the levels of adaptive response in bystander cells between cultured in radiation conditioned and in non-radiation conditioned medium from 10% to 24%. Moreover, the expression of SOD2 of bystander cells decreased after culture in radiation-conditioned medium for 3 h and 5 h compared with that cultured in non-radiation-conditioned medium. The results suggested that the conditioned medium from unirradiated cells induced an adaptive response to X-irradiation in bystander cells, and that from irradiated cells caused a greater adaptive response. TGF-β1 pathway played an important mediating role in the occurrence of the response, but SOD2 was not involved.Cited