OBJECTIVE: To optimize the formulation of Cilnidipine sustained-release tablet, and study its drug-release mechanism. METHODS: Solvent method was adopted to prepare the cilnidipine solid dispersion, then Cilnidipine sustained-release tablet was prepared by using hypromellose K4M (HPMC K4M) as release material. Using comprehensive scores of cumulative release degree in 2, 6, 12 h as indexes, single factor method and Box-Behnken response surface method were used to screen the amounts of HPMC K4M and ethyl cellulose (EC), lactose-microcrystalline cellulose (MCC) ratio in formulation of Cilnidipine sustained-release tablet, and verification test was conducted. The drug-release mechanism of Cilnidipine sustained-release tablet was investigated by model fitting way. RESULTS: The optimal formulation was as follow as 25% of cilnidipine solid dispersion, 30% of HPMC K4M, 10% of EC, lactose-MCC ratio of 1 ∶ 1 (m/m). The adhesive was 5% PVPP ethanol solution and the lubricant was 0.5% magnesium stearate. The cumulative release degrees of prepared sustained-release tablet in 2, 6, 12 h were (21.4±3.3)%, (62.9±2.8)%, (85.4±0.5)% (n=3), relative error of which to predicted value 25%,60%,90% were 14.4%,4.8% and 5.1%. Release curve showed the highest fitting degree with the first-order release model, conforming to non-Fick diffusion. CONCLUSIONS: Cilnidipine sustained-release tablet with sustained-release effect is successfully prepared by optimized formulation.