Concentrated growth factors (CGF) is the newest generation platelet concentrate product, which has been reported to promote the proliferation and differentiation of human dental pulp cells (hDPCs). However, the effect of liquid phase of CGF (LPCGF) has not been reported. This study was aimed to evaluate the influence of LPCGF on the biological properties of hDPCs, and to explore the in vivo mechanism of dental pulp regeneration based on the hDPCs-LPCGF complex transplantation. It was found that LPCGF could promote the proliferation, migration and odontogenic differentiation of hDPCs, and 25% LPCGF induced the most mineralization nodule formation and the highest DSPP gene expression. The heterotopic transplantation of the hDPCs-LPCGF complex resulted in the formation of regenerative pulp tissue with newly formed dentin, neovascularization and nerve-like tissue. Together, these findings provide key data on the effect of LPCGF on the proliferation, migration, odontogenic/osteogenic differentiation of hDPCs, and the in vivo mechanism of hDPCs-LPCGF complex autologous transplantation in pulp regeneration therapy.