Nickel oxide nanoparticles were synthesized by microemulsion method and characterized by powder X-ray diffraction, dynamic light scattering, and scanning electron microscopy. Thermal analyses were performed to identify the influence of nickel oxide nanoparticles on the in situ combustion of Liaohe heavy oil. Low-temperature oxidation and coking process were investigated by analysing the effluent gases and the fractions of saturates, aromatics, resins, and asphaltenes. Combustion tube tests were also conducted to evaluate the catalytic performance of nickel oxide nanoparticles. Compared with the runs without catalysts, the effective activation energies were reduced by 4.22%, 20.57%, and 35.75% in terms of low-temperature oxidation, pyrolysis, and high-temperature oxidation, respectively. The reduction in O-2 fraction and the increase in CO2 and O-2 uptake were also confirmed. The overall trend presented the increase of saturates and aromatics fraction and the decline of resins and asphaltenes fraction while temperature was increased during low-temperature oxidation. Adding nickel oxide nanoparticles led to the reduction in the fuel deposit during pyrolysis. Compared with the base combustion tube runs, combustion time in catalytic experiment was shortened by 12.1%, combustion front movement was accelerated by 9.1%, oil recovery was enhanced by 4.0%, and oil viscosity was reduced by 61.2%.