To elucidate the conformational behavior of DNA, an integrative approach by combining experimental and computational methods is developed. In the experimental part, the forward and backward titration are conducted to measure the folding and unfolding processes of a giant DNA by increasing and decreasing PEG concentration, respectively, at a high salt concentration (to screen out DNA charges). We find that these two processes form a hysteresis loop, suggesting that the folding and unfolding processes of a giant DNA undertake different pathways. The results present the very first experiment to characterize the conformational hysteresis loop of DNA. Furthermore, computer simulations are resorted to examine the role of chain semiflexibility on hysteresis loop by using a bead-spring chain model. The simulations predict that the hysteresis loop emerges only when the chain is stiff enough, but not in the case of flexible chains. Meanwhile, the compact conformation in the hysteresis loop is found to be thermodynamically more stable. Nevertheless, the elongated DNA chain, which is thermodynamically less stable, persists until the concentration of condensing agents becomes high enough. Such behavior can be attributed to the semiflexibility of a DNA molecule. Namely, an increase of chain stiffness attenuates the number of chain conformations, including most of conformations required to make a transition to compact conformation. As a result, the folding process is impeded. On the contrary, an increase of condensing agent concentration enhances monomer-monomer attraction, which facilitates the folding process by increasing the number of chain conformations.