Objective A novel multi-mode thermoresponsive chiral stationary phase （Sil-NP-NCAD） functionalized with cellulose derivative and N-isopropylacrylamide copolymers was prepared through a surface-initiated atom transfer radical polymerization reaction （ATRP）. Methods The intermediate and final products Sil-NP-NCAD were characterized by elemental analysis and infrared spectroscopy. To elucidate the multiple retention mechanisms of the prepared column，the correlations between retention time of analytes and the composition of the mobile phase and the column temperature were studied. Results The results showed that the prepared stationary phase exhibited a good separation selectivity to five nucleosides （thiourea，uridine，adenosine，adenine and cytosine） and four anilines （diphenylamine，benzidine，m-phenylenediamine and p-phenylenediamine）. The selectivity of these compound could be modulated by regulating the column temperature. The chiral separation of warfarin was also achieved. Conclusion These results indicated that the thermoresponsive chiral stationary phase can be a potential tool for separation of hydrophilic chiral drugs.