A general approach for selective, differential functionalization of the interior and exterior surfaces of mesoporous Si is reported. The method employs two immiscible liquids, one inert and the other chemically reactive with the porous Si nanostructure. First, a porous Si sample is prepared by electrochemical etch and then it is mildly oxidized, which places a thin layer of silicon oxide at the surface. The inner pore walls of the partially oxidized porous Si film are then infiltrated with an inert liquid (octane). The sample is then immersed in aqueous solution containing hydrogen fluoride (HF), which serves as the reactive liquid. The hydrophobic phase is retained in the interior of the porous nanostructure, and HF(aq) attacks only the exposed surfaces of the oxidized porous Si sample, generating a hydrophobic, hydrogen-terminated (Si-H) outer layer. The reaction is self-limiting due to the immiscibility of octane and water, and the extent of penetration of the Si-H surface into the porous layer is dependent on the time of exposure to HF(aq). The Si-H surface can then be modified by thermal hydrosilylation (1-dodecene or 10-bromo-1-decene) in a subsequent step, resulting in a bifunctional porous Si film containing hydrophobic pore entrances to hydrophilic inner pores. The hydrophobic dodecyl species at the mouths of the pores is found to form a barrier for molecular transport; it decreases the rate of leaching (into water) of a rhodamine test molecule that is preloaded into the sample by >8 fold.