Following the principle of single-atom catalysts (SACs), the fourth-period transition metals (TM) were designed as active sites on a MoSi2N4 monolayer surface with N vacancy, and the catalytic mechanisms of these single-atom active sites for the conversion of CO2 to CO were investigated by first-principles calculations. Our results showed that the doped TM atoms on the MoSi2N4 surface significantly enhanced the CO2 reduction reaction (CO2RR) activity compared with the pristine MoSi2N4 monolayer. Our findings after analyzing all the doped structures in our work were as follows: (1) the Sc-, Ti-, and Mn-doped structures exhibited very low limiting potentials; (2) out of Sc-, Ti- and Mn-doped structures, the Mn@MoSi2N4-Nv structure showed the best catalytic performance with a limiting potential of only -0.16 V, exhibiting an advantage over the hydrogen evolution reaction, which is a competitive reaction of CO2RR. However, the positive binding free energy at 298.15 K of the intermediate reactant *COOH on the Mn@MoSi2N4-Nv surface indicated its unstable state, which hinders the CO generation process. This is contrary to the results derived from the adsorption/binding energy at 0 K, which indicated that the effect of temperature cannot be ignored when considering adsorption/binding energy. Our work provides insights into the effects of temperature on the catalytic mechanisms for CO2RR through TM-doped MoSi2N4 monolayers.