Candida rugosa lipase (CRL) was encapsulated via the sol-gel method, using 5, 11, 17, 23-tetra-tert-butyl-25, 27-bis(2-aminopyridine)carbonylmethoxy-26, 28-dihy-droxy-calix[4]arene-grafted magnetic Fe3O4 nanoparticles (Calix-M-E). The catalytic activity of encapsulated lipase (Calix-M-E) was tested both in the hydrolysis of p-nitro-phenyl palmitate (p-NPP) and the enantioselective hydrolysis of racemic naproxen methyl ester. The present study demonstrated that the calixarene-based compound has the potential to enhance both reaction rate and enantiose-lectivity of the lipase-catalyzed hydrolysis of racemic naproxen methyl ester. The encapsulated lipase (Calix-M-E) had great catalytic activity and enantioselectivity (E > 400), as well as remarkable reusability as compared to the encapsulated lipase without supports (E - 137) for S-Naproxen. © Springer-Verlag Berlin Heidelberg 2013.