Due to their large anti-Stokes shifts, sharp emission spectra and long excited-state lifetimes, upconversion nanoparticles (UCNPs) have attracted an increasing amount of research interests, and have shown great potential for enhancing the practical utility of gene therapy, whose versatility has been limited by existing gene delivery technologies that are basically mono-functional in nature. Despite this, up to now in-depth analysis of the development of UCNPs for gene delivery has been scant in the literature, even though there has been an upsurge of reviews on the chemistry of UCNPs and their applications in bioimaging and drug delivery. To fill this gap, this review aims to present the latest advances in the development and applications of UCNPs as gene carriers. Prior to describing the prominent works published in the field, a critical view on the properties, chemistry and molecular design of UCNPs for gene delivery is provided. With a synopsis of the recent advances in UCNP-mediated gene delivery, challenges and opportunities could be illuminated for clinical translation of works in this nascent field of research.