Provided are a method of and apparatus for lossless video encoding and decoding, in which a differential residual block generated by calculating a difference between pixels of a residual block resulting from interprediction is encoded, thereby improving the compression rate. The method of lossless video encoding includes performing interprediction between a reference frame and a current frame in units of a predetermined-size block to generate a predicted block of a current block to be encoded, generating a residual block composed of residual signals corresponding to differences between pixels of the predicted block and the current block, calculating differences between the residual signals of the residual block in a predetermined direction and generating a differential residual block based on the calculated differences, and performing entropy-encoding on the differential residual block.