〔Abstract〕 Objective To investigate the differential expression of long noncoding RNA(LncRNA) gene in the regeneration of skull defects in young sheep and its effects in improving skull defects. Methods Twelve 1-month-old small-tailed Han sheep were divided into the primary bone tissue group and the skull defect group, with 6 in each group. High-throughput sequencing was used to detect the expression changes of LncRNA in the two groups of bone tissues, and Real-time PCR was used to verify the changes in the expression of sequencing LncRNA. The serum alkaline phosphatase(ALP) and osteocalcin(OCN) were detected by ELISA. The protein expression levels of Wnt and β-catenin were detected by Western blot. Results The expressions of LncRNA ODSM and LncRNA UCA1 were up-regulated, while the expressions of LncRNA H19 and LncRNA MEG3 were down-regulated in the new bone tissue; the content of ALP and OCN in serum of the new bone group increased; the expression of Wnt/β protein in bone increased compared with the original bone tissue group. Conclusion LncRNA ODSM and UCA1 may regulate Wnt/β signaling pathway and participate in the regeneration of skull tissue at the defect site.