The study was performed to investigate the molecular mechanism for SCI patients. The interaction between miRNA-130a and HDAC was demonstrated in PBMCs from SCI patients. Increased HDAC3 and decreased miRNA-130a were observed in PBMCs from AS patients. Next, HDAC3 loss-of-function or HAAC3 inhibition promoted the expression of miRNA-130a, and HDAC3 could be recruited to the promoter region of the gene, miRNA-130a, in PBMCs. In addition, linear regression analysis indicated that mRNA expression results were highly negative correlated between HDAC3 and miRNA-130a in PBMCs from SCI patients. Furthermore, miRNA-130a down expression increased the expression of HDAC3 in PBMCs. Loss-of-function of miRNA-130a promoted PBMCs apoptosis, but HDAC3 loss-of-function had no significant effect on the apoptotic cell. In addition, miR-130a overexpression decreased, whereas miR-130a inhibition increased, the expression of TNF-α in PBMCs. Furthermore, HDAC3 loss-of-function or HAAC3 inhibition associated with simultaneous up-regulation the expression of miR-130a and down-regulation the expression of TNF-α in PBMCs. In conclusion, HDAC3 regulated a distinct underlying molecular and pathogenic mechanism of SCI by forming a negative feedback loop with miR-130a and enhanced TNF-1α expression.