Virus-mediated gene delivery has been, to date, the most successful and efficient method for gene therapy. However, this method has been challenged because of serious safety concerns. Over the past decade, mesoporous silica nanoparticles (MSNs) have attracted much attention for intracellular delivery of nucleic acids. Delivery of cellular plasmid DNA (pDNA) is designed to replace the function of a defective gene and restore its normal function in the cell. Delivery of small interfering RNAs (siRNAs) can selectively knockdown genes by targeting specific mRNAs. The biocompatibility and unique structures of MSNs make these nanoparticles ideal candidates to act as biomolecule carriers. This concise review highlights current progress in the field of nucleic acid delivery using MSNs, specifically for delivery of pDNA, siRNA, and combinatorial delivery of nucleic acids and drugs. The review describes important design parameters presently being applied to MSNs to administer drugs and therapeutic nucleic acids.