Spinal cord injury (SCI) is a severe disable symptom and has posed a great health threat to many people. Circ-HIPK3 has been reported to modulate the biological behavior of neuronal cells. Thence, in this study, we explored the mechanism of circ-HIPK3 in affecting functions of neuronal cell in SCI. SCI rat model was constructed to evaluate the apoptosis condition of spinal cord tissue. Meanwhile, 100 mM of CoCl2 was used to treat AGE1.HN and PC12 cells to induce in vitro SCI model. Functional assays were implemented to investigate the apoptosis of AGE1.HN and PC12 cells. RNase R and Act D treatment were both conducted to verify the circular character of circ-HIPK3. In this study, circ-HIPK3 was found lowly expressed in SCI rat models and AGE1.HN and PC12 cells induced by 100uM of CoCl2. Meanwhile, inhibited circ-HIPK3 or overexpressed circ-HIPK3 could separately elevate or reduce the apoptosis of AGE1.HN and PC12 cells. Moreover, circ-HIPK3 was identified as the ceRNA against miR-558 to up-regulate DPYSL5. Circ-HIPK3/miR-558/DPYSL5 axis modulated the apoptosis of AGE1.HN and PC12 cells in SCI. In conclusion, circ-HIPK3 relieves the neuronal cell apoptosis through regulating miR-588/DPYSL5 axis in SCI. (C) 2020 Elsevier Inc. All rights reserved.