Abstract: Multiple input multiple output (MIMO) sky-wave over-the-horizon radar (OTHR) transmits the wide beams with low gain at the transmitter, and achieves receiver beam-forming to get narrow beams with high gain. The MIMO technique is an ideal choice for OTHR to detect the target through the multi-layer ionosphere and suppress the strong clutters. This paper applies a two-layer ionospheric model in MIMO-OTHR, and proposes a mutual information method to adaptively optimize the waveforms in order to suppress strong clutters with high clutter-to-noise ratio (CNR). Numerical experiments show that this method improves range resolution and detection probability significantly. It also demonstrates that, by applying the optimization method, the multipath propagation can be utilized to enhance the radar performance.