This study was for verifying that transfecting colon cancer cells (CCCs) with lncRNA NEAT1 packed with siRNA chitosan nanoparticles (CNPs) can suppress lncRNA NEAT1 and biological behaviors of the cells. siRNA targeting lncRNA NEAT1 expression vector was constructed and then transfected into CCCs after being packed with CNPs. Subsequently, the impact of the transfection on biological behaviors of the cells was evaluated. As a result, with high expression in CCCs, NEAT1 was negatively bound up with miR-377-3p in cases with colon cancer (CC), and dual luciferase reporter assay confirmed the potential binding region. Additionally, after downregulating NEAT1 in CCCs, transfection of NEAT1 siRNA packed with CNPs brought a great inhibition on cell proliferation and a promotion on apoptosis, and inhibiting miR-377-3p was able to offset the role of silencing NEAT1 in CCCs. Therefore, in our opinion, NEAT1 siRNA packed with CNPs can hinder the growth and metastasis of CCCs by knocking down NEAT1 in CC, and its mechanism may be achieved by targeting miR-377-3p, which offers a novel direction for treating CC.