Emerging evidence suggests that microRNAs (miRNAs) play key roles in the regulation of multiple biological processes, including the differentiation of osteoblasts. Although miRNA‐based gene therapy holds immense potential in the treatment of a variety of diseases, the intracellular delivery of miRNA remains challenging owing to the lack of efficient and safe gene carriers. In this study, a fluoropolymer (FP) is constructed through the modification of polyamidoamine (PAMAM) using heptafluorobutyric anhydride and then is used as a carrier for miR‐23b transfection to induce osteocyte differentiation of osteoblasts. The derivative FP is found to facilitate miR‐23b transfection due to its favorable endosomal escape from the "proton sponge" effect. Compared to PAMAM/miR‐23b, the FP/miR‐23b nanocomplex efficiently promotes the differentiation of osteoblasts and formation of calcified nodules, attributable to enhanced expression of various osteogenesis genes (runt‐related transfection factor 2 [RUNX2], alkaline phosphatase [ALP], osteopontin [OPN], and osteocalcin [OCN]). Thus, FP‐mediated miR‐23b transfection may be used as an effective strategy to facilitate osteogenic differentiation.