Hyperlipidemic acute pancreatitis (HAP) is a serious inflammatory pancreatic disease commonly seen in patients with disorders of lipid metabolism. Decreasing blood triglyceride levels and proinflammatory factors can alleviate hyperlipidemic pancreatitis. The lipase that enhanced the Brownian motion of mesoporous silica in triglyceride solutions could accelerate decomposition of the lipid and improve the efficiency of absorption. In this study, we developed a mesoporous silica nanoparticle with dual modification of IL-6 aptamer and lipase for the treatment of HAP. The nanoparticle could increase the ability of particles to absorb inflammatory factor IL-6 and decompose triglycerides. For every 10 mg of the dual-modified nanoparticles, the efficiency of capturing IL-6 was approximately 9.67 pg/mL and of decomposing triglycerides was approximately 3.88 mg/mL in the plasma of HAP patients within 2 h. In summary, the mesoporous silica nanoparticle could absorb the IL-6 inflammatory factor through IL-6 aptamers and decompose triglycerides through lipase. Furthermore, based on clinically available plasma exchange technology, combined with our developed dual-modified nanoparticles, we designed an absorption device for the treatment of hyperlipidemic pancreatitis; it works to promote the treatment of hyperlipidemic pancreatitis.