By performing global-switching on-the-fly trajectory surface-hopping molecular dynamics simulation at the OM2/MRCI (14,15) quantum level, we probed the S3(ππ*) photoisomerization mechanisms associated with excited-state intramolecular hydrogen transfer for 2′-hydroxychalcone (2HC) within the interwoven conical intersection networks from four singlet electronic states (S3, S2, S1, and S0). The simulated quantum yields of 0.03 forcis-to-transand zero fortrans-to-cisphotoisomerization were due to almost all the conical intersections being localized either in thecis-2HC or intrans-2HC region, and there was little chance for sampling trajectories to reach the rotation conical intersection (S1/S0) in betweencis-2HC andtrans-2HC that is key for reactive isomerization. The potential energy well on the S1state in thetrans-2HC region prevents trajectories fromtrans-to-cisphotoisomerization, while the fact there is no well on S1state incis-2HC region opens a few chances for trajectories to reach the rotation conical intersections. The present simulation found that excited-state intramolecular hydrogen transfers in 2HC have a negative impact for reactive isomerization, and that hydrogen transfers take place on the S1state, while back-transfer on the S0state prevents sampling trajectories reaching rotational conical intersections. It was realized that it could be possible to enhance the quantum yield of 2HC photoisomerization by suppressing the hydrogen transfer (such as by changing an electron-donating substitution or adjusting the substitution position to decrease the acidity of the phenol group). From a perspective view of the potential energy surfaces, the theoretical design of such 2HC derivatives could enhance (control) the quantum yield by shifting the conical intersections away from thecis- andtrans-region.