Half-metallic NiCo2O4 with high spin polarizability has great potential applications in spintronics. The manipulation of magnetic anisotropy is crucial for spintronics based on spin-transfer or spin–orbit torques, as it is directly related to the critical switching current density. Here, we report epitaxial growth of metallic NiCo2O4 film with perpendicular magnetic anisotropy on MgAl2O4 single crystal substrates. The modulation of the magnetic anisotropy was achieved by changing the growth conditions (deposition temperature and thickness) of NiCo2O4 films and by means of protonation. Strong dependence of magnetic coercivity on deposition temperature (350–500 °C) has been observed due to variable phase configuration. Furthermore, the magnetic coercive field can also be effectively controlled by the film thickness (3–78 nm) through strain relaxation. More importantly, spin reorientation transition has been achieved by proton and electron doping in the NiCo2O4 films, resulting in reconfigured valence states of Ni and Co cations and a magnetic easy axis rotation from out-of-plane to in-plane. The effective modulation of the magnetic anisotropy provides important insights into the functional design of NiCo2O4-based spintronics with ultralow energy dissipation.