The possibility of substitution reactions is investigated on a block copolymer film attached to a crystalline surface by epitaxial adsorption. The epitaxial film is made by a technique of polymerization-induced epitaxy, in which polymerization reactions induce epitaxial adsorption of growing chains. A crystalline block is synthesized first so that it is grown epitaxially to provide a binding unit to the substrate surface. Then, a non-crystalline block containing a chemically modifiable group is copolymerized onto the crystalline block. A thin film is obtained by simply rinsing the surface thoroughly with good solvents of the polymer to wash away spontaneously adsorbed polymers. Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy and scanning tunneling microscopy were used to characterize the insoluble film of poly(tetrahydrofuran)-block-co-poly(tetrahydrofuran-random-co-3,3-bis(chloromethyl)oxacyclobutane) on a basal plane of graphite, and to follow a substitution reaction of chlorine with an azide. This study demonstrates that the film tethered by epitaxy can be modified by ordinary chemical reactions without disintegrating the film nor damaging the substrate surface.