Folic acid (or folate, FA) has attracted considerable attention for cancer therapy. As one small molecule, its receptor (folate receptor, FR) is significantly overexpressed on the surface of many human tumor cells compared with normal cells. In this work, physical and chemical coupled modification method, that is the combination of nanoimprinting technique and graft polymerization, was adopted to modify FA on nanopatterned polydimethylsiloxane (PDMS) surface for possible application in micro-nanofluidic cytology. The surface property of differently treated PDMS was characterized by FTIR, AFM and contact angle measurement. AO/PI double staining, cell counting and MTT method were performed to examine the potential influence of FA modified nanopatterned PDMS on human cervical carcinoma (HeLa) cell behavior. Both FA modification and nanostructure have positive effect on the growth and viability of HeLa cells. It is the first time that the small molecule-folic acid was used to immobilize on the surface of PDMS in order to improve its surface property.