The van der Waals SiC/MoS2 heterostructure with a type-II band alignment is promising for potential applications in photocatalytic and optoelectronic devices. By performing time-dependent nonadiabatic molecular dynamics simulations, we study the dynamics of single sulfur and carbon vacancy-mediated of photoexcited hole transfer at the interface of SiC/MoS2. The results indicate that single C-vacancy in SiC atomic layer promotes interlayer hole transfer more sufficiently in a shorter timescale of 68 fs than those of S-vacancy and pristine heterostructures. This promotion is attributed to the decreased energy gap related to intralayer hole transfer in SiC layer, resulting from the split of acceptor state, the excitation of a stronger in-plane carbon atom vibration mode at 600 cm−1, and the enhancement of electron–phonon coupling. Meanwhile, electron-hole recombination is three orders of magnitude slower than hole transfer, ensuring an effective charge separation in SiC/MoS2 with C-vacancy. This work provides theoretical insights into the dynamics of photoexcitation hole transfer in MoS2/SiC heterostructure.