Long noncoding RNA (lncRNA) is a new key regulatory molecule in the occurrence of osteoporosis, but its research is still in the primary stage. In order to study the role and mechanism of lncRNA in the occurrence of osteoporosis, we reannotated the GSE35956 datasets, compared and analyzed the differential expression profiles of lncRNAs between bone marrow mesenchymal stem cells (hBMSCs) from healthy and osteoporotic patients, and then screened a lncRNA RAD51-AS1 with low expression in hBMSCs from osteoporotic patients, and its role in the occurrence of osteoporosis has not been studied. We confirmed that the expression level of lncRNA RAD51-AS1 in hBMSCs from patients with osteoporosis was significantly lower than those from healthy donors. A nuclear cytoplasmic separation experiment and RNA fluorescence in situ hybridization showed that RAD51-AS1 was mainly located in the nucleus. RAD51-AS1 knockdown significantly inhibited the proliferation and osteogenic differentiation of hBMSCs and significantly increased their apoptosis, while RAD51-AS1 overexpression significantly promoted the proliferation, osteogenic differentiation, and ectopic bone formation of hBMSCs. Mechanistically, we found that RAD51-AS1 banded to YBX1 and then activated the TGF-β signal pathway by binding to Smad7 and Smurf2 mRNA to inhibit their translation and transcription up-regulated PCNA and SIVA1 by binding to their promoter regions. In conclusion, RAD51-AS1 promoted the proliferation and osteogenic differentiation of hBMSCs by binding YBX1, inhibiting the translation of Smad7 and Smurf2, and transcriptionally up-regulated PCNA and SIVA1.