Context: Delirium in cancer is often difficult to control and refractory when haloperidol is invalid which is considered standard therapy. We need second and subsequent-line therapy to reduce hyperactivity and not to over-sedation for refractory delirium. Objectives: To investigate the efficacy and safety of continuous subcutaneous infusion chlorpromazine on delirium refractory to first-line antipsychiatric medications in advanced cancer palliative care setting. Method: The study population consisted of patients who received continuous subcutaneous infusion chlorpromazine for delirium at two certified PCU. Primary endpoint was the proportion of patients who showed improvements in delirium severity by Delirium Rating Scale Revised 98 score of less than 13 or decrease from baseline and maintained the ability to communicate coherently by Communication Capacity Scale Item-4 score of 2 or less. Secondary outcome were the Nursing Delirium Screening Scale subscale score, and injection site reactions evaluated according to the Common Terminology Criteria for Adverse Events. These outcome measures were assessed at baseline, 48 hours and 7 days after the start of the study. Result: Among eighty-four patients, sixty were positive responders (71.4%, 95% CI [61–80]). The mean CCS Item-4 scores significantly decreased from the baseline value of 1.48 (range 0–3) to 1.03 (range 0–3) at post-treatment (p<0.001). Grade 2 or higher injection site reactions were observed in 1 patient (1.2%, 95% CI [0–7]). Conclusion: Our study suggested that continuous subcutaneous infusion chlorpromazine could improve refractory delirium symptoms and patients’ communication capabilities. Although most of the skin disorders observed in association with chlorpromazine were mild, their incidence rates were relatively high, suggesting the need for careful monitoring.