An apparatus and a method for canceling interference using a space-frequency block coding in a multi-antenna system. The method includes confirming a code for coding to minimize a Pairwise Error Probability (PEP) of a transmit signal of which the PEP is maximized according to a time variation; and coding the transmit signal with the code and transmitting the coded signal via at least two antennas. Accordingly, the interference cancellation can be accomplished while lowering the complexity of the receiver without degrading the spectral efficiency.