The invention discloses an optical interconnection substrate applied to a spacecraft and a military computer and a manufacturing method thereof. The optical interconnection substrate comprises a transmitting component, a receiving component and an LTCC (Low Temperature Co Fired Ceramic) substrate provided with a cavity, the cavity of the LTCC substrate is internally provided with a single side polished silicon wafer, and a polishing surface of the silicon wafer is provided with a composite waveguide; one end of the composite waveguide is provided with a first reflector, and the other end of the composite waveguide is provided with a second reflector; another side of the LTCC substrate is assembled with a VCSEL (Vertical Cavity Surface Emitting Laser) device in the transmitting component and a PD (Potential Difference) device in the receiving component, a first micro-lens array is arranged between the VCSEL device and the first reflector, and a second micro-lens array is arranged between the PD device and the second reflector. The LTCC optical interconnection substrate provided by the invention has the characteristics of being smaller in volume, lighter in weight and higher in integration density, thereby being applicable to manufacturing the spacecraft and the military computer, and being easier to realize an assembling process of a photoelectric component.