A high-efficacy, long-acting formulation of silibinin, comprising silibinin solid dispersion, silibinin-loaded silica nanoparticles, slow-release matrix material and release enhancer, wherein the mass ratio of these components is silibinin solid dispersion:silibinin-loaded silica nanoparticles:slow-release matrix material:release enhancer=1:0.5˜1.25:0.1˜0.3:0.1˜0.3； the drug loading rate of the said silibinin-loaded silica nanoparticles is 51.29˜51.77%； the said silibinin solid dispersion contains povidone K30, soybean lecithin, acrylic resin IV, wherein the mass ratio between silibinin and other medical accessories is silibinin:povidone K30:soybean lecithin:acrylic resin IV=1:1˜3:0.3˜0.8:0.2˜0.5. Compared with the existing formulations, the half life of the high-efficacy, long-acting formulation of silibinin disclosed in this invention is 14.8 times longer while the mean residence time (MRT) of which is 4.52 times longer； when tested in vivo in Beagle dogs, this new formulation of silibinin presents a smoother concentration-time curve and reaches the continuous release for 72 hours. This invention discloses its preparation method.
