Polymerization reactions are prone to runaway risks due to the unstable nature of monomers and the complex interactions between reactants. The major direct cause of polymerization runaway incidents is the deviation from the standard recipe or designed operation conditions. These unintended reactions may lead to auto-accelerated temperature and pressure rise, followed by rupture of reaction vessels, fire, and explosion. To minimalize the risk, the polymerization reaction runaway behavior under various hazardous scenarios should be fully identified and carefully quantified. The understanding of the thermal/pressure behaviors and mechanisms during thermal runaway is essential to facilitate safer handling and storage of the reactive styrene system. In this work, three most credible hazardous scenarios have been identified regarding the styrene system during polymerization and storage, including the deviation in monomer mass fraction, the deviation in initiator type and concentration, and the contact between monomer and a variety of impurities. Runaway hazards of these scenarios were calorimetrically investigated. Lumped kinetic models have been developed to predict reaction hazards. Calorimetric results showed that the onset of the runaway reaction was strongly affected by the co-existing chemicals in the polymerization recipe. Polymerization inhibitor retarded the initial stage of the runaway reaction. The mischarging of the solvent had a complex effect on the runaway hazards of the polymerization reaction, as the addition of solvent monotonically reduced temperature-related thermal hazards and increased the pressure hazards. Experiment and thermodynamic calculations indicated that volatile diluent increased system vapor pressure even at a lower adiabatic temperature rise. The mischarging effect of two different radical initiators, including benzoyl peroxide (BPO) and azobisisobutyronitrile (AIBN), was investigated at a series of elevated concentrations in both screening and adiabatic calorimeters. The onset temperature shifted to lower values with higher initiator dosage in the system. The overall heat generation, pressure building-up rate monotonically increased with initiator concentration. Finally, screening calorimeters were employed to quantify the contamination effects of styrene in contact with impurities, including water, alkaline, and acid. The exothermic characteristics of styrene mixed with contaminating substances were significantly related to the impurity concentrations and mixing conditions, especially for strong acids.