Background: The study aimed to explore the efficacy of oblique lateral interbody fusion (OLIF) combined with Wiltse approach pedicle screw fixation in the treatment of single-level degenerative lumbar spondylolisthesis(DLS).Methods: This is a retrospective study. The study enrolled 54 patients with single-level DLS who were treated at the Affiliated Jiangnan Hospital of Zhejiang Chinese Medical University from May 2018 to June 2020. (OLIF group) 24 cases operated using OLIF combined with Wiltse approach pedicle screw fixation, and (PLIF group) 30 cases operated by PLIF. The primary outcome measures were visual analog scale (VAS) pain scores, Oswestry dysfunction index (ODI), and the lower lumbar spine anterior convexity angle. The secondary outcome measures were operation time, intraoperative blood loss, postoperative drainage, hospitalized days, intervertebral space height, and postoperative complications. Results: All patients were followed up for 12-20 months, with a mean of 16.2 months. There were significant differences in VAS (2.63±0.58 vs 3.57±0.63, P<0.001) and ODI (9.67±0.92 vs 10.63±1.40, P<0.05) between the OLIF group and PLIF group on postoperative days (PODs) 1–3. However, the differences in VAS and ODI between the two groups were not significant at 6 months postoperatively. And there was a significant decrease in VAS (2.63±0.58 vs 1.08±0.28, P<0.05) and ODI (3.57±0.63 vs 1.10±0.31, P<0.05) in both groups in the PODs 1–3 and 6-month postoperative comparisons. OLIF group showed better intervertebral space height and the lower lumbar spine anterior convexity angle scores on PODs1–3 and at 6 months postoperatively.Conclusion: OLIF combined with the Wiltse approach pedicle screw fixation can achieve good short-term clinical results in the treatment of single-level DLS. This surgical approach is less invasive, promotes early functional recovery, shortens hospitalization time, and improves the quality of life.