Abstract:[Objective] To observe the expression of Necdin (NDN) gene in osteosarcoma, and to explore its relationship with clinico- pathological factors and prognosis of osteosarcoma. [Methods] A retrospective study was performed on 51 patients who received neoadju- vant chemotherapy, as well as tumor segment resection and prosthetic reconstruction after osteosarcoma was confirmed by biopsy in our hos- pital from October 2009 to July 2019. The clinical outcomes, NDN expression in tissue were evaluated. [Results] All the 51 patients were followed up for more than 38 months, with survival time of 78 months in the longest and 16 months in the shortest. During the follow-up, 16 patients got local recurrence and 33 patients had metastasis. At the latest follow-up, 10 patients were of survival with tumor-free (STF) , 5 patients of survival with tumor (ST) , and 36 patients died (death) . In term of grouping comparison based on the outcome at the latest followup, the proportion of stage IIB and stage III in the death group was significantly higher than that in the tumor-free survival group and the tu- mor-bearing survival group (P<0.05) , and the death group had significantly higher ratio of lung metastasis than the STF and ST groups (P< 0.05) . However, there were no significant differences in terms of age, gender, tumor size and NDN expression among the three groups (P> 0.05) . The positive rate of NDN immunohistological staining was of 29.41% (15/51) in osteosarcoma tissues, whereas 80% (8/10) in normal bone tissues around the tumor, which was statistically significant (P<0.05) . As results of Kaplan-Meier survival analysis and log-rank test, the mean survival time proved significantly different in terms of different Ennecking stage, lung metastasis, tumor size and NDN (P<0.05) . With regarding to Cox analysis, the Ennecking stage (HR=1.530) , lung metastasis (HR=4.662) and tumor size (HR=3.398) were risk factors for survival, while positive NDN (HR=0.207) were protective factors for survival. [Conclusion] The osteosarcoma tissue has significantly lower positive NDN expression than the adjacent normal bone tissue. The worsened preoperative Ennecking stage, lung metastasis and tu-mor ≥5 cm are risk factors for poor prognosis of osteosarcoma, while positive NDN expression is a protective factor.