Abstract: OBJECTIVE To study the formulation and process parameters of Olanzapine tablets. METHODS The HPLC was used to assay the content of olanzapine and related compounds in Olanzapine tablets, and the real-time dissolution test apparatus of drug was used to determine the dissolution profile of Olanzapine tablets. The definitive screening design was used to optimize Olanzapine tablets' formulation and process parameters. RESULTS Intragranular or extragranular microcrystalline cellulose and the amount of hydroxypropyl cellulose in fomulation influenced the distribution of granule size significantly. The amount of hydroxypropyl cellulose in fomulation and the stirring speed in granulating significantly influenced the f₂ of dissolution profile in vitro between the generic Olanzapine tablets and the RLD. The optimized formulation of Olanzapine tablets was 2.5% of olanzapine, 78% of lactose, 10% of intragranular microcrystalline cellulose, 4% of hydroxypropyl cellulose, 5% of PVPP-XL, 0.5% of magnesium stearate. The optimized granulation process was 3 rps (stirring speed), 30 rps (cutting speed) and 5 min (granulation time). CONCLUSION The definitive screening design can be used to optimize Olanzapine tablets' formulation and process parameters. The dissolution profiles in vitro of Olanzapine tablets prepared according to the optimized formulation and process are similar with the RLD, and they meet the regulations of Chinese Pharmacopoeia 2015 on content uniformity and related compounds.