Background: Polyhydroxyalkyl furans are important bioactive compounds that have been extensively studied in organic chemistry. In this work, a green and chemoselective process for the synthesis of polyhydroxyalkyl furans from unprotected sugars and malononitrile was developed. Results: Under optimal conditions (sugar (1 mmol), malononitrile (1 mmol), water (1 mL), Novozym 435 (200 U,13.2 mg), 60 degrees C, 6 h), high isolated yields of polyhydroxyalkyl furans (79 %-92 %) could be obtained when Novozym 435 was used as the catalyst, and no by-product was found in this system. Moreover, 76 % yield of polyhydroxyalkyl furan could be obtained even after six cycles. Thus, Novozym 435 exhibits satisfactory chemoselectivity and good reusability in this reaction. Conclusion: This enzymatic method demonstrates the great potential for the synthesis of polyhydroxyalkyl furans and extends the application of enzyme catalytic promiscuity in organic synthesis.