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This study aimed to investigate the effects of nanohydroxyapatite–silica–glass ionomer cement (nanoHA–silica–GIC) on the differentiation of dental pulp stem cells (DPSCs) into odontogenic lineage. DPSCs were cultured in complete Minimum Essential Medium Eagle—Alpha Modification (<i>α</i>-MEM) with or without nanoHA–silica–GIC extract and conventional glass ionomer cement (cGIC) extract. Odontogenic differentiation of DPSCs was evaluated by real-time reverse transcription polymerase chain reaction (rRT–PCR) for odontogenic markers: dentin sialophosphoprotein (<i>DSPP</i>), dentin matrix protein 1 (<i>DMP1</i>), osteocalcin (<i>OCN</i>), osteopontin (<i>OPN</i>), alkaline phosphatase (<i>ALP</i>), collagen type I (<i>COL1A1</i>), and runt-related transcription factor 2 (<i>RUNX2</i>) on day 1, 7, 10, 14, and 21, which were normalized to the house keeping gene glyceraldehyde-3-phosphate dehydrogenase (<i>GAPDH</i>). Untreated DPSCs were used as a control throughout the study. The expressions of <i>DSPP</i> and <i>DMP1</i> were higher on days 7 and 10, that of <i>OCN</i> on day 10, those of <i>OPN</i> and <i>ALP</i> on day 14, and that of <i>RUNX2</i> on day 1; <i>COL1A1</i> exhibited a time-dependent increase from day 7 to day 14. Despite the above time-dependent variations, the expressions were comparable at a concentration of 6.25 mg/mL between the nanoHA–silica–GIC and cGIC groups. This offers empirical support that nanoHA–silica–GIC plays a role in the odontogenic differentiation of DPSCs.