Unsaturated polyester resin (UP) is a critical polymer material in applications of many fields, such as the chemical industry, military, and architecture. For improving the mechanical properties, some hardeners, such as methyl ethyl ketone peroxide (MEKPO) or tert-butyl peroxy-2-ethylhexanoate (TBPO), can trigger the curing reaction in UP polymerization, which causes that UP changes the structure from monomer to polymer. However, polymerization is a strong exothermic reaction, which can increase the risk of thermal runaway reaction in UP. Therefore, the mechanisms and characteristics in the thermal runaway reaction of UP mixed with hardeners should be studied for preventing and controlling UP explosion. The thermal hazards of UP mixed with hardeners were determined by thermogravimetric analyzer (TGA) and differential scanning calorimetry (DSC) analysis. According to the results, UP mixed with MEKPO exhibited a more violent mass loss and exothermic reaction than UP mixed with TBPO. Furthermore, the thermal runaway reactions of UP mixed with MEKPO or TBPO with different mixing proportions of 1:1, 3:1, and 5:1 were determined. Irrespective of MEKPO or TBPO, the mixing proportions of 3:1 exhibited a high onset temperature and low enthalpy of curing reaction (ΔHexo). This demonstrated that this proportion was safer during UP polymerization. The results of this study can provide useful information for preventing UP explosion and developing polymerization technology.