<p>The selection of working fluid is very important for the application and development of thermodynamic cycle system. Due to the flammability of HFO-1234ze(E) and HFC-32, this study investigated the combustion mechanism and product characteristics of their mixture using ReaxFF reactive molecular dynamics and density functional theory (DFT) calculations. In the combustion reaction, HFO-1234ze(E) initially undergoes a synergistic elimination reaction to generate HF, followed by HFC-32 and O₂ participating in the reaction. HFO-1234ze(E) preferentially generates HF through synergistic elimination reaction (accounting for 29.32% of the reaction pathway), and its decomposition rate is significantly faster than HFC-32. The early release of F radicals can quickly capture H atoms, effectively suppress chain reactions, and thus inhibit the combustion of HFC-32. The generation of the main products HF, CO, and CO₂ (via CFO intermediates) is temperature dependent: at high temperatures (&gt;2000 K), CO₂ decreases due to decomposition, and early intervention is needed to advance the peak of COF₂. The apparent activation energies of HFO-1234ze(E) and HFC-32 are 34.14 kJ/mol and 31.17 kJ/mol, respectively. This study is of great significance for promoting the development of efficient and low GWP thermal systems, and providing a theoretical basis for the safe design of related equipment.</p>