In this study, we investigated the effects of Ti and Nb additions on the grain size of prior austenite and mechanical properties such as yield strength, yield ratio, and impact toughness in quenched and tempered AISI 4145 steel. It was found that the grain size of prior austenite directly influenced the mechanical properties. Thermodynamic calculations were carried out to find the characteristics of the precipitates such as dissolution temperature of precipitates, the average size of precipitate particles, precipitate fraction, and mean distance among precipitate particles, quantitatively. A specimen with low Ti content had a smaller Ti/N ratio than the stoichiometric ratio of 3.42 and showed an effective inhibition of grain growth of prior austenite, whereas a specimen with high Ti content showed a little effect to prevent the austenite grain growth compared with a Ti-free sample. Based on the thermodynamic simulation, the (Nb, Ti) (C, N) complex was precipitated and contributed to the inhibition of austenite grain growth, resulting in not only higher yield strength and yield strength/tensile strength ratio but also improved toughness.