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.