The invention relates to a prestressed hollow composite slab and a manufacturing method thereof, and belongs to the field of normal building construction. The composite slab comprises prefabricated pieces (1) and composite layers (2). Thickness of a bottom plate (3) of each prefabricated piece (1) is greater than or equal to 35 mm and less than or equal to 60 mm, prestressed steel wires (4) in the bottom plate are located at the upper parts of transversal steel bars (5), and the length of each prestressed steel wire (4) and each transversal steel bar (5) extending out of the corresponding bottom plate (3) is greater than or equal to 50 mm; the width of each prefabricated piece is greater than or equal to 1500 mm, light-weight material filling pieces (6) are arranged at the upper part of each prefabricated piece (1); the heights of concrete solid ribs (7) between adjacent filling pieces are greater than or equal to 50 mm; the transversal steel bars (5) between adjacent prefabricated pieces (1) are overlaid in a joint area (8), upper part steel bars (10) of the composite slab are bound, composite layer concrete is poured, and the composite slab is formed. According to the prestressed hollow composite slab and the manufacturing method thereof, the self-weight of the composite slab is light, the stiffness in the longitudinal direction and the transversal direction is high, the application range is large, and transportation and installation are convenient. The prestressed hollow composite slab and the manufacturing method thereof have good economic efficiency and applicability, and play a role on promoting the development of building technology.