As an analogue of the main protein contained in naturally formed nacre, reconstituted silk fibroin (SF) from the Bombyx mori silkworm silk shows a strong preference for the formation of the aragonite form of CaCO3 crystals and allows fine control over their size and morphology. The aragonite phase could be generated via two different routes: direct growth or dissolution and recrystallization, depending on the concentration of Ca2+ and SF. Generally, lower concentrations of Ca2+ and SF favor the formation of aragonite needles and their aggregates, of which the lattice structure of the precursor is similar to that of the organic matrix in natural shell. Higher concentrations lead to the formation of aragonite aggregates via a dissolution and recrystallization process through intermediates of lens-like vaterite. Molecular modeling shows that the β-strand conformers of silk fibroin molecules has an excellent match with the ionic spacing in the aragonite (010) plane, which can promote growth along the (001) long axis of aragonite crystals. This synergy between silk fibroin and the aragonite phase may help our understanding of the function of organic matrices involved in the biomineralization process, and facilitate the fabrication of synthetic materials with the potential for high performance mechanical properties.