An apparatus and a method for canceling interference based on Maximum Likelihood (ML) at a receiver of a multi-antenna system are provided. The method includes estimating a channel using a signal received over one or more receiver antennas; generating one or more weights using the estimated channel to cancel interference; detecting a candidate symbol having the shortest Euclidean distance through Maximum Likelihood using a first weight; and soft-decoding the candidate symbol using a second weight. Therefore, by receiving the signal based on the ML under the interference, the system capacity can be increased and the reception performance can be enhanced.