Rationale:Diagnosing and treating refractory cancer pain have become standardized and effective procedures with guidance from the Expert Consensus on Refractory Cancer Pain released in 2017 by the Committee of Rehabilitation and Palliative Care of China. Doxorubicin has been used for perineural injection in the treatment of chronic non-cancer pain owing to its retrograde sensory ganglion resection effect. Our study reports a new fourth-ladder treatment for cancer pain: CT-guided paravertebral doxorubicin injection for patients with refractory cancer pain caused by paraspinal metastasis.Patient concerns:A 48-year-old female and a 47-year-old male patients suffered from refractory cancer pain over the past months. They had both undergone surgical tumor resection, chemotherapy, and precision radiotherapy but result in limited analgesic effect. The daily oral morphine dosage was around 60 to 100mg and rescue analgesic methods had been used at the time.Diagnoses:Refractory cancer pain in 2 patients with renal cancer and hepatobiliary adenocarcinoma.Interventions:The patients both received computed tomography (CT)-guided 1mL of 0.5% doxorubicin paravertebral injection at each affected nerve root segments.Outcomes:The Visual Analog Scale and Douleur Neuropathique four Questions were used for 6-month follow-up, and the analgesic requirement was also recorded. The patients enjoyed satisfactory analgesia for up to 6 months without adverse reaction. In addition, the oral opioid analgesic doses were significantly reduced after the neurolytic block.Lessons:The CT-guided paravertebral doxorubicin injection was an effective fourth-step analgesic interventional technology that allowed our 2 patients with refractory cancer pain to maintain satisfactory analgesia. This analgesia method taken at an appropriate stage, according to the latest analgesic concept, results in good analgesia and opioid use reduction. Also, with the imaging guidance, only a small amount of neurolytic agent is needed to achieve analgesia in a precise and safe way.