The aim of this study was to develop and characterize a self-microemulsifying drug delivery system (SMEDDS) of Brucea javanica oil (BJO) and transform the liquid formulation into solid granules. Solubility studies of BJO and pseudo-ternary phase diagrams were used to identify the most efficient self-emulsification region. A methyl thiazolyl tetrazolium (MTT) assay was performed to identify cell apoptosis. Antitumor activity studies were also employed to evaluate the BJO SMEDDS. The optimized BJO SMEDDS in liquid and granule formulations rapidly formed fine oil-in-water microemulsions with particle sizes <50 nm. Additionally, the MTT assay demonstrated that BJO SMEDDS had a significant effect on cancer cells, and antitumor activity studies showed remarkable inhibition of S180 tumors. The BJO SMEDDS, optimized to have good characteristics, was successfully transformed into solid granules by adsorbing onto crospovidone. The studies of the release of the BJO SMEDDS of liquid and granules in vitro suggested that the release of BJO was enhanced by the SMEDDS. These studies revealed that the new self-microemulsifying systems of liquid and granule forms might be promising strategies for the oral delivery of the poorly water-soluble drug BJO.