naf·cil·lin (n?f?s?l??n)n. A semisynthetic penicillin, C21H22N2O5S, that is resistant to penicillinase, used in the form of its sodium salt primarily to treat infections caused by penicillinase-producing staphylococcus bacteria.[naf- (shortening and alteration of naphthalene) + (peni)cillin.]American Heritage® Dictionary of the English Language, Fifth Edition. Copyright © 2016 by Houghton Mifflin Harcourt Publishing Company. Published by Houghton Mifflin Harcourt Publishing Company. All rights reserved.