Vascular endothelial growth factor (VEGF)-A is a potential signaling protein that may promote angiogenesis. VEGF also helps cells survive in stressfull or hazardous conditions. The present study aimed to compare the effect of VEGF with translationally controlled tumor protein (TCTP), an anti‑apoptotic protein in human dental pulp cells (HDPCs), following exposure to 2‑hydroxyethyl methacrylate (HEMA), which is a major residual monomer from resin restorative dental materials. Cell viability, alkaline phosphatase (ALP) activity, mineralization and gene expressions for odontogenic and osteogenic differentiation markers of HDPCs were investigated, following exposure to HEMA and in combination with TCTP and VEGF. The results revealed that TCTP at 1 ng/ml and VEGF at 10 ng/ml significantly promoted the proliferation of HDPCs (P<0.05). TCTP (1 ng/ml) and VEGF (10 ng/ml) maintained the cell viability of 4 mM HEMA‑treated cells at the same percentage as the control. However, cells treated with HEMA+TCTP+VEGF had a lower cell viability than the groups treated with HEMA and TCTP or VEGF alone. TCTP and VEGF promoted cell proliferation, ALP activity and mineralization, and upregulated of DSPP, DMP‑1, BMP‑2, and ALP mRNA expression compared with the control. Furthermore, the HEMA+TCTP and HEMA+VEGF groups had significantly higher percentages of calcium deposition than HEMA‑treated cells (P<0.001). HEMA was cytotoxic to HDPCs, reduced ALP activity and caused the significant downregulation of odontogenic and osteogenic gene expressions (P<0.05). It was concluded that VEGF and TCTP promoted pulp cell growth and the survival of HEMA‑treated cells without synergistic effects. TCTP was required in lower concentrations for these effects. VEGF and TCTP enhanced cell differentiation and mineralization.