Objective To analyze the clinical efficacy and safety of collagenase and oxyen-ozone intradiscal injection for the treatment of lumbar disc herniation in patients with Grade I degenerative spondylolisthesis. Methods　Forty-nine patients who suffered lumbar disc herniation with grad I spondylolysis were therapeutic allianced　by the intradiscal injection of collagenase and oxyen-ozone　under the guidance of CT. Clinical effects were evaluated by observing the changes of visual analogues scales (VAS), taking painkillers and the distance of the sliding vertebrae, and evaluated by using modified Macnab method on postoperative day-7 and at final follow-up (6 months after surgery). Results　All patients were punctured and operated successfully. The distance of the sliding vertebrae had no significant difference at all the time. Compared with preoperative clinical data, the VAS score and score of taking painkillers both dropped significantly (P<0.05). The effective rate that we evaluated by using modified Macnab were 85.71% on postoperative day-7 and 87.76% 6 months after surgery. There were no postoperative complications in all patients. Conclusion　Injecting collagenase combined with oxyen-ozone by the CT-guided can relieve pain, which has no influence of sliding vertebrae. The radicular symptoms were remarkably improved in most patients immediately after surgery. It is a safe, effective and minimally invasive method for treatment of lumbar disc herniation in patients with Grade I degenerative spondylolisthesis.