Airway smooth muscle cell proliferation contributes to airway remodeling, a key feature of asthma. The mechanisms that control smooth muscle cell proliferation are not fully understood. Nesprin-1 (also called SYNE-1) connects with actin filaments with its N-terminus. The C-terminus of nesprin-1 interacts with Sad1p and UNC84 (SUN) protein that links to the nucleoskeleton. It has been thougt that nesprin-1 plays a role in mechanotransduction between the actin cytoskeleton and the nucleoskeleton solely. In this study, we found that expression of nesprin-1 was upregulated in asthmatic human airway smooth muscle (HASM) cells. In addition, signal transducers and activators of transcription 3 (STAT3) is essential for the regulation of cell proliferation. The role of nesprin-1 in STAT3 nuclear import has not been previously investigated. Here we used RNAi and immunofluorescence microscopy to assess the effects of nesprin-1 knockdown (KD) on STAT3. Nesprin-1 KD attenuated STAT3 nuclear import in HASM cells upon activation of platelet-derived growth factor (PDGF). Furthermore, nesprin-1 KD inhibited cell proliferation as evidenced by cell counting and the BrdU incorporation assay. Moreover, NUP62 is a component of the nuclear pore complex that is crutucak for cargo import to the nucleus. PDGF stimulation increases the colocalization of nesprin-1 and NUP62. Together, these results unveil a new role of nesprin-1 in smooth muscle cell proliferation. Mechanistically, stimulation with growth factors enhances the interaction of nesprin-1 with NUP62, which may facilitate STAT3 nucelar translocation and cell proliferation.