The electronic properties of sphalerite (110) surface with Zn-vacancy and S-vacancy were calculated by using density-functional theory, and the effects of vacancy defect on the copper activation of sphalerite were investigated. The calculated results indicate that surface state occurs in the band gap of Zn-vacancy sphalerite, which is from the contribution of S 3p orbital at the first layer of the surface. The presence of S-vacancy results in surface state appearing near the Fermi level and the bottom of conductor band, which are composed of S 3p and Zn 4s orbital, respectively. The surface structure of Zn-vacancy sphalerite is more stable than S-vacancy surface due to the occupation of Zn-vacancy by Cu atoms; hence, the substitution reaction of Cu for Zn vacancy is easier than the substitution of Cu for Zn atoms with S-vacancy surface.