Lipid-coated calcium phosphate (LCP) nanoparticles (NPs) are proven to be effective vehicles for the delivery of genes and some drugs, while it is not desirable for NPs to release genes/drugs in late endosomes/lysosomes. To achieve the early endosomal release and escape, we have designed and developed new lipid-coated calcium carbonate/phosphate (LCCP) hybrid NPs. These new hybrid LCCP NPs have a spherical structure with an average diameter of 40 nm and high gene loading capacity. We particularly demonstrate that the loaded dsDNA/siRNA is mostly released under mildly acidic conditions (pH 6.0-5.5). LCCP NPs are also effectively internalized by B16F10 cells in a dose and time dependent way. The delivery efficacy has been further demonstrated using two functional siRNAs, i.e. programmed death ligand 1 (PD-L1) siRNA for PD-L1 silencing and polo-like kinase 1 (PLK1) siRNA for growth inhibition of B16F10. Consistently, the LCCP loaded PD-L1 siRNA shows quicker PD-L1-mRNA inhibition than LCP NPs, indicating that LCCP NPs improved the siRNA release in endosomes.