The invention discloses a preparation method of raw validamycin powder. The preparation method comprises the steps of centrifuging a validamycin fermentation solution at a high speed to remove mycelium; filtering the centrifugal liquid by using a ceramic micro-filtration membrane with the aperture of 1-10mu m; then, adding nanosilicon dioxide, nano aluminum oxide, thermoplastic acrylic resin and a surfactant with the HLB (Hydrophile-Lipophile Balance) value of 15-20 into the filtrate according to a certain weight, stirring for 10-30min, and regulating the pH value of the filtrate to 7.5-8.5; filtering by a hollow fiber ultrafiltration membrane of which the molecular cut off is 10000-20000 Dalton, collecting the filtrate, carrying out activated carbon decoloration, concentrating and drying to obtain the raw validamycin powder. The preparation method is capable of preparing the raw validamycin powder with high validamycin A and validamycin B contents, high in ultrafiltration efficiency and long in service life of the ultrafiltration membrane. In addition, the preparation method has the characteristics of simple steps, short production period, high efficiency and the like.