This study was to assess the clinical efficacy of epidural injections with tumor necrosis factor-alpha (TNF-α) inhibitor in patients with chronic radicular pain caused by lumbar spinal stenosis (LSS). In a randomized controlled trial (RCT), patients diagnosed with mild-to-moderate LSS underwent epidural intervention with three different drugs and were allocated to TNF-α inhibitor group (Group A), steroid group (Group B) and lidocaine-only group (Group C). All patients were evaluated by visual analog scale (VAS) for leg pain and Oswestry disability index (ODI) to assess function. They all received a 6-month follow-up. Ninety patients were randomly assigned to three groups, for 30 cases in each group. A total of 82 participants (91.1%) completed the follow-up. Pain relief and improvement of movement function after epidural administration in Group A were more significant than those of groups B and C ( < .05) during the 6-month follow-up, while it showed no significant difference between groups B and C ( > .05). Our results indicated that epidural administration with TNF-α inhibitor may be a useful conservative method for the treatment of radicular pain caused by LSS. ClinicalTrials.gov Identifier: NCT04062474.