Abstract: OBJECTIVE To prepare the taste masked flucloxacillin sodium granules and evaluate the quality. METHODS The formulation and preparation process were optimized by single factor test by using release profile and particle size as index. RESULTS The optimum formulation and process were as follows: the proportion of remedium cardinal, behenic acid glycerol ester and sodium carboxymethyl starch was 10∶15∶0.5; the proportion of citric acid and sucralose was 1∶3, and the usage was 1%; the temperature of the material was 67 ℃; the atomization pressure was 0.2-0.25 MPa; the spray velocity was 10-15 r·min^-1. The particle size of the optimal product was about 100 mesh. Compared with the brand-name drug, it had 5 min of hysteresis effect, but the level of its release was 85% at the 15 min. CONCLUSION The optimal product can meet the requirement of bitterness covering, and in vitro release.