Enhancement of a heat transfer rate of mixed convection flow in a three-dimensional vertical channel with insertion of a moving slender block is investigated numerically. A slender block is installed along the direction of the channel flow, and the movement of the slender block is in periodic motion and transverse to the channel flow. The interaction between the moving block and the channel flow destroys and suppresses the velocity and thermal boundary layers on the heat surface periodically. Various ratios of the Richardson numbers (Gr/Re2) are simulated. The results show that under a higher velocity of the channel flow and a lower magnitude of Gr/Re2, the enhancement of heat transfer rate is better. Oppositely, under a lower velocity of the channel flow and a higher magnitude of Gr/Re2, the effect of natural convection driven by the buoyancy force is stronger and it is unfavorable to the heat transfer. A counter effect of the heat transfer rate is observed. These phenomena which are seldom analyzed before by numerical simulation are carried out in this study.