The flammability limits of the hydrogen-oxygen mixture are extremely wide, and the ignition energy is low. Due to its excellent combustion properties, the hydrogen-oxygen mixture can be used as fuel in internal combustion engines (ICEs). However, the combustion of hydrogen-oxygen mixture is too intense, which results in limited research on its application in ICEs and is limited to low-temperature conditions in aerospace. This research aims to numerically discuss the coupling effects of equivalence ratio and ignition timing on the port fuel injection hydrogen-oxygen ICE under the low-temperature intake condition. The three-dimensional geometric model of a single-cylinder ICE was established using the CONVERGE software and validated against the mean in-cylinder pressure and reaction mechanism. The results indicate that adjusting equivalence ratio and ignition timing operating parameters is beneficial for controlling the temperature and pressure in the cylinder within a reasonable range during the total combustion process. In general, under the low-temperature intake condition, adopting a high equivalence ratio and optimal ignition timing strategy improve the combustion process and power performance of the port fuel injection hydrogen-oxygen ICE.