DNA–RNA hybrid (DRH) plays important roles in many biological processes. Here, we use a thermodynamic theory to analyze the free energy and unpeeling properties of the overstretching transition for the DRH molecule and compare the results with double-helix DNA. We report that the RNA strand of DRH is easier to get unpeeled than the DNA strand while the difficulty in unpeeling the double helix DNA lies in between. We also investigate the sequence effect, such as GC content and purine content, on the properties of unpeeling the DRH. Further, to study the temperature effect, the force-temperature phase diagram of DRH and DNA are calculated and compared. Finally, using a kinetic model, we calculate the force–extension curves in the DRH stretching and relaxation process under different pulling rates and temperatures. Our results show that both pulling rate and temperature have important infl uences on the stretching and relaxation kinetics of unpeeling the DRH. Putting all these results together, our work provides a comprehensive view of both the thermodynamics and kinetics in DRH overstretching.