Hormetic responses generally refer to biphasic dose-response relationships showing low-dose stimulation and high-dose inhibition (Calabrese and Baldwin, Hum. Exp. Toxicol., 2002, 21, 91-97; Calabrese and Linda, Nature 2003, 421, 691-692; Calabrese, Environ. Toxicol. Chem. 2008, 27, 1451-1474). In relation, “photon hormesis” refers to the phenomenon in which a low-dose photon irradiation mitigates the cellular damages induced by other ionizing radiations (Rithidech and Scott, Dose Response 2008, 6, 252-271). “Photon hormesis” can mean gamma-ray hormesis or X-ray hormesis depending on the origin of the photons, and gamma-ray hormesis has been proposed as an explanation for the suppression of lung cancers induced by alpha particles (Scott, Dose Response 2008, 6, 299-318; Scott et al. J. Am. Physicians Surg. 2008, 13, 8-11). In the present study, X-ray hormesis was demonstrated in CHO and HeLa cell lines by comparing the number of p53 binding-protein 1 (53BP1) foci per cell occurred in the cells which were (1) irradiated by a toxic dose of alpha particles from an ²⁴¹Am source, and (2) irradiated by the same dose of alpha particles with an additional small X-ray dose (10 mGy). With the additional X-ray dose, the numbers of 53BP1 foci per cell were significantly reduced at 24 h post-irradiation, which confirmed the presence of X-ray hormesis. Moreover, photon hormesis was also studied using HCT116 and HCT 116 p53-/- cells using the methodology described above, which showed that p53 played an important role in the photon hormesis.