The invention discloses a preparation method of anti-cancer traditional Chinese medicine sugarless granules, belongs to the technical field of medicine, and relates to Chinese patent drugs. The preparation method comprises the following steps: (1) accurately weighing the following ingredients in parts by weight: 5 parts of radix scutellariae, 4 parts of epimedium, 5 parts of grossy privet fruit, 4 parts of fleece-flower root, 4 parts of rehmannia, 3 parts of radix rubiae, 4 parts of rhizoma polygonati, and 1 part of ginseng; (2) mixing radix scutellariae and ginseng to obtain a mixture, smashing the mixture, and carrying out extraction according to a supercritical CO2 extraction method; (3 ) extracting medicine residue according to a microwave method; (4) mixing longspur epimedium, grossy privet fruit, rehmannia, radix rubiae, rhizoma polygonati, and fleece-flower root to obtain a mixture I, smashing the mixture I to obtain powder, mixing the power with the medicine residue, adding water for soaking, and carrying out decoction; (5) combining the extract liquor, the extraction solution, and the decoction solution, filtering, adding an ethanol solution, allowing standing still for sedimentation to remove substances which are insoluble in ethanol, and concentrating under reduced pressure to obtain clear paste; (6) producing particles from the clear paste according to the conventional method, and drying to obtain the anti-cancer traditional Chinese medicine sugarless granules. The preparation method is high in medicine extract rate, relatively low in impurity content in the extraction solution, and high in medical bioavailability.