Purpose To investigate the short-term clinical effect of collagenase chemonucleolysis (CCNL) in the treatment of residual pain after transforaminal lumbar endoscopic discectomy (TLED). Patients and Methods The clinical data of 40 patients with residual pain after TLED for lumbar disc herniation (LDH) in our hospital from January 2018 to December 2020 were retrospectively analyzed. The visual analogue scale (VAS) and quality of recovery-15 (QoR-15) were used to evaluate the effect of the operation. Modified MacNab method was used to evaluate the efficacy of CCNL at 6 months and 12 months after operation. Results All patients successfully completed the operation without serious complications, such as intervertebral space infection, vascular injury and nerve injury. The VAS 3 days after TLED was not significantly lower than that Pre-TLED (P > 0.05). The VAS at each time point after CCNL was significantly lower than that at Pre-TLED, and the QoR-15 score at each time point after CCNL was significantly higher than that 3 days after CCNL (P < 0.05). The modified MacNab criteria for the last follow-up was 95%. Conclusion CCNL can effectively relieve the residual pain after TLED, and the quality of life of patients after TLED is improved with time, and the safety of CCNL is higher.