Enhancement of flow boiling in microchannels through adjusting surface structures has attracted much attention in recent years. However, most of the existing studies focus on homogeneous surface structures. In the present study, a novel vertical microchannel with pillar–cavity mixed structures is conceived to enhance flow boiling heat transfer. In the mixed microchannel, cavities and pillars are distributed on the vertical sidewalls of the upstream and downstream flow channel, respectively. A multicomponent phase-change lattice Boltzmann model is employed to investigate the flow boiling performance of the mixed microchannel. Numerical results show that the cavities in the mixed microchannel can supply effective nucleation sites for timely departure of bubbles, while the pillars in the mixed microchannel can suppress the expansion of the vapor film from the outlet toward the inlet. Moreover, the bubbles from the upstream cavities can entrain the cold liquid to disrupt the vapor film covering the downstream pillars for the rewetting of the heated surface. As a result, the flow boiling performance can be significantly enhanced by the synergistic effect of the pillar and cavity structures, and the best flow boiling performance can be achieved by controlling the ratio of the number of cavities to the total number of structures in the mixed microchannel to optimize the synergistic effect. The influences of the structural parameters of pillars and cavities on the flow boiling performance have also been studied. It is found that the height of the pillars and the depth of the cavities have important influences on the flow boiling performance, while the boiling performance is not sensitive to the width of the pillars.