Objective To prepare follicle stimulating hormone (FSH) polypeptide modified nanoparticles (NP) in order to achieve specific ovarian tumor targeting. Methods Expression of FSH receptor protein in human liver cancer and ovarian cancer cell lines BEL-7402, SKOV-3 and Caov-3 was detected by immunocytochemistry. The polypeptide fragment of FSH β 81 -95 amino acids (FSHL81-95)was synthesized and covalently coupled to NP. The specific binding of FSHL81-95 and FSHL81-95-NP was examined by fluorescence microscopy and flow cytometry. Results BEL-7402 and SKOV-3 cells were negative for FSH receptor staining, while Caov-3 celia were positive. The diameters of NP were about 100 nm, with a Zeta potential of -25 mV or so. Caov-3 cells showed a more specific interaction with FSHL81-95-NP than SKOV-3 cells (4. 17 ± 0. 86 and 2. 30 ± 0. 21 ; P < 0. 05). The uptake of FSHL81-95-NP was more than NP in Caov-3 cells (4. 17 ± 0. 86 and 0. 41 ± 0. 32 ; P < 0. 05 ). FSHL81-95-NP showed a selective targeting at Caov-3 cells compared with control NP. Conclusion FSH polypeptide modified NP could selectively target ovarian cancer cells expressing FSH receptor, which might contribute to specific endocytosis mediated by FSH receptor.