The effective work functions and formation energies for Ni/HfO2 interfaces with and without defects, including interfacial intrinsic atom substitution and atom vacancy in interfacial layer were studied by first-principles methods based on density functional theory (DFT). The calculated results of the formation energies indicate that the interfaces with O-Ni combining bonds in the interfacial region are more energetically favorable and a small amount O vacancy is comparatively easy to form in O-Ni interface, especially under O-rich situation. Moreover, the results of our calculations also reveal that, (1) the effective work functions strongly depend on the type of interface, interface roughness and atom substitution content in the interface region; (2) for Hf-Ni interfaces, two calculated effective work functions without and with Ni substitutions in whole interfacial Hf layer are good for nMOS and pMOS effective work function (EVVF) engineering, respectively; (3) the EWFs are sensitive to Hf vacancy rather than Ni vacancy in interfacial layer for Hf Ni interfaces; (4) oxygen vacancies can result in a decrease of effective work function for O-Ni interfaces. Additionally, we establish an expected theoretical relationship that variations of the EWFs are in proportion to that of interface dipole density. Finally, ionic valence state and occupied state are used to qualitatively analyze and explain the effects of interfacial defects on the EWF in metal-oxide interfaces. Our work suggests that controlling interfacial intrinsic atom substitution and interface roughness are attractive and promising ways for modulating the effective work function of Nil HfO2 interfaces. (C) 2016 Elsevier B.V. All rights reserved.