A single-carrier multiple-input multiple-output (MIMO) system with frequency-selective channels suffers from the inter-symbol interference (ISI) and the co-channel interference (CCI). To eliminate both type of interference, we propose in this letter a hybrid two-stage decision-feedback equalizer (HTS-DFE), which performs the frequency-domain equalization (FDE) in the first stage and the layered serial interference-cancellation (SIC) in the second stage. Since the decision-feedback (DF) or noise-prediction (NP) architecture can be employed in FDE or SIC, the proposed equalizer actually can have four variations that achieve the same mean square error (MSE) under the assumption of perfect feedback. Further, we combine HTS-DFE with the decoded decision-feedback (DDF) scheme to mitigate the error-propagation encountered in the practice. Simulation results confirm that the proposed HTS-DFE can outperform the existing equalizers significantly.