Sr1-xLaxTiO3 (SLTO) ceramics with colossal permittivity were fabricated by conventional solid-state reaction method. The point defects of pure STO and SLTO ceramics were analyzed by Positron Annihilation Lifetime Spectroscopy (PALS) and Coincidence Doppler Broadening (CDB). The charge compensation mechanisms and dielectric properties of ceramics were investigated. The results indicated that the intrinsic defects in pure STO ceramics were mainly VTi″″. The charge compensation mechanism of SLTO ceramics was predominantly formation of VSr″. With increasing La content, εr of SLTO ceramics increased up to ∼70000 at room temperature. The results of first-principle calculations indicated that the colossal permittivity came from a sharp polarization increase caused by dipole structure of defects. tanδ of SLTO ceramics showed obvious Debye relaxation at high temperatures and the relaxation showed a multiple relaxation times derived from different kinds of polarization mechanism. The main polarization mechanism of SLTO ceramics gradually changed from ion displacement polarization to defect dipole polarization influenced by the concentration of La dopants.