Sputtering targets of CIGS quaternary ceramic were fabricated by hot-press sintering the milled powder mixture of Cu₂Se, In₂Se₃ and Ga₂Se₃. When the milling time of the powders less than 4 h, the sintered targets delaminated, while the delamination disappeared with the prolonging milling time. Therefore the physico-chemical changes of the powder mixture during the milling process and their influence on the delamination of the targets were investigated. The results indicate that with the progress of the milling process, mechanical alloying (MA) occurred, and chalcopyrite Cu(In, Ga)Se₂ (CIGS) formed from Cu₂Se, In₂Se₃ and Ga₂Se₃; With the increasing milling time, CuInSe₂ (CIS) formed on the surface of binary copper selenide firstly and CIGS was subsequently generated due to the inward diffusion of Ga; Thus the original blend powders became a mixture of CIGS and residual Ga₂Se₃ after milling for 48 h. Since CIGS and Cu_2-xSe have a similar crystallographic structure, therefore this epitaxial relation may facilitate the formation of CIGS. The disappearance of Cu-Se binary compound and the formation of CIGS restrained the delamination of the CIGS targets in the sintering process.