The invention discloses a three-dimensional semiconductor device comprising a plurality of memory unit transistors and a plurality of selection transistors, wherein the plurality of memory unit transistors are at least partially overlapped in the vertical direction; each selection transistor comprises a first drain electrode distributed along the vertical direction, an active region, a common source electrode formed in a substrate and a metal grid electrode distributed around the active region; each memory unit transistor comprises a channel layer distributed vertical to the surface of the substrate, wherein a plurality of interlayer insulating layers and a plurality of grid electrode stacking structures are alternately stacked along the side wall of the channel layer, and a second drain electrode is located at the top of the channel layer; the channel layer is electrically connected with the first drain electrode. According to the three-dimensional semiconductor device and a manufacturing method thereof disclosed by the invention, multi-grid MOSFETs (Metal-Oxide-Semiconductor Field Effect Transistors) are formed below memory unit string stacks comprising vertical channels so as to be used as the selection transistors, thus the threshold voltage control characteristic of the grid electrode is improved, the off-state leakage current is reduced, the over-etching for the substrate is avoided, and the reliability of the device is effectively improved.