Calcium phosphate cements (CPCs) are a unique class of inorganic injectables attractive for the repair and regeneration of hard tissues. Tailoring the crystallite properties of CPC, particularly to represent nanotopological features, is favorable for stimulating biological reactions. Nanotopological tailoring has recently been achieved on CPCs by simply modulating the sizes of the initial particles. Herein, we aim to investigate the effects of nanotopological-tailored CPCs on the odontogenic differentiation of stem cells derived from human dental pulp (HDPSCs) as well as on their implicated signal pathways. The initial adhesion of the cells was substantially higher on nano-CPCs than on micro-CPCs. A series of indications of odontogenesis, including alkaline phosphatase activity and gene expressions (dentin matrix protein-1, dentin sialophosphoprotein, osteocalcin, ostepontin, and bone sialoprotein) were significantly stimulated on the nano-CPC in comparison to the micro-CPC. Furthermore, the integrin downstream pathways of the cells, including FAK, paxillin, Akt, MAPK, and NF-kappa B, were highly activated on the nano-CPC with respect to those on the micro-CPCs. Collectively, the nanotopological CPCs significantly enhance the odontogenic differentiation of HDPSCs when compared to conventional micro-CPCs through the integrin-associated signaling pathways, which implies that the nanotopological CPCs may be more potent in the repair and regeneration of dentin-pulp complex tissues.