In this research, the photon interaction of NaI:Tl, LiI:Tl and CsI:Tl scintillators have been comparative studied. The photon interaction effectiveness of scintillators was investigated by determine mass attenuation coefficient (m) and half value layer (HVL) at photon energy ranging 1 keV – 100 GeV using WinXCom computer software program. Build–up factors were computed by Geometric Progression (G–P) fitting formula at energy ranging 15 keV – 15 MeV up to 40 mfp penetration depth. The result shown that, CsI:Tl scintillator was excellent at interacting with photons. This study indicated that CsI:Tl can be developed for radiation detectors and sensors.