PCBM (a C-60 derivative) is so far the most successful electron acceptor for bulk-heterojunction polymer photovoltaic (PV) cells. Here we present a novel method epitaxy-assisted creation of PCBM nanocrystals and their homogeneous distribution in the matrix using freshly cleaved mica sheet as the substrate. The highly matched epitaxy relationship between the unit cell of PCBM crystal and crystallographic (001) surface of mica induces abundant PCBM nuclei, which subsequently develop into nanoscale crystals with homogeneous dispersion in the composite film. Both the shape and size of these nanocrystals could be tuned via choosing the type of matrix polymer, film thickness, ratio of PCBM in the composite film, and annealing temperature. Thus, the obtained thin composite film is removed from the original mica substrate via the flotation technique and transferred to a real substrate for device completion. The success of this method has been verified by the substantially improved device performance, in particular the increased short-circuit current, which is heavily dependent on the morphology of the photoactive layer. Therefore, we have actually demonstrated a novel approach to construct preferred morphology for high-performance optoelectronic devices via resorting to other specific substrates which could induce the formation of this type morphology.