The receiver’s architecture is always a critical issue in multiple-input multiple-output (MIMO) systems, as it has a great impact on the system’s performance and complexity. Accordingly, in this paper, a spectral decomposition-based minimum mean squared error (MMSE) receiver is proposed in an uplink multi-user MIMO (MU-MIMO) system with a full-duplex decode and forward relay. Imperfect channel state information is assumed at the relay and base station where, least-squares channel estimation technique is applied due to its simplicity and low complexity. An equivalent relay is applied for self-interference cancellation. While, multi-user interference is mitigated by using the block diagonalization concept. A closed-form expression for the mean squared error (MSE) of the estimated data symbol is derived in the presence of channel estimation error. Moreover, an optimization problem is solved to derive an expression for the proposed MMSE receiver’s matrix. Finally, the performance of the proposed receiver is compared to that of the conventional receiver and Zero-forcing (ZF) receiver. Results show the superiority of the proposed receiver over both receivers.