Combined in-band full duplex-multiple input multiple output (IBFD-MIMO) technology can significantly improve spectrum efficiency and data throughput, and has broad application prospects in communications, radar, the Internet of Things (IoT), and other fields. Targeting the self-interference (SI) issue in microwave photonic-based IBFD-MIMO communication systems, a microwave photonic self-interference cancellation (SIC) method applied to the narrowband 2 × 2 IBFD-MIMO communication system was proposed, simulated, and analyzed. An interleaver was used to construct a polarization multiplexing dual optical frequency comb with a frequency shifting effect, generating a dual-channel reference interference signal. The programmable spectrum processor was employed for filtering, attenuation, and phase-shifting operations, ensuring amplitude and phase matching to eliminate the two self-interference (SI) signals. The simulation results show that the single-frequency SIC depth exceeds 45.8 dB, and the narrowband SIC depth under 30 MHz bandwidth exceeds 32.7 dB. After SIC, the desired signal, employing a 4QAM modulation format, can be demodulated with an error vector magnitude (EVM) as low as 4.7%. Additionally, further channel expansion and system performance optimization are prospected.