Dyspnea is one of the most distressing symptoms in patients with advanced cancer. Although systemic opioids are recommended as first-line pharmacologic treatment, 30-50% of patients do not achieve adequate relief. Midazolam is often used for persistent dyspnea despite opioid administration; however, robust evidence supporting its efficacy as a second-line treatment remains limited. To evaluate the feasibility of a randomized controlled trial assessing the efficacy and safety of continuous subcutaneous midazolam infusion as second-line treatment for persistent dyspnea despite morphine administration in hospitalized patients with advanced cancer. A protocol for a multicenter, randomized, double-blind, placebo-controlled feasibility trial (J-SUPPORT2201/JORTC-PAL22) is described. The trial is being conducted at nine sites in Japan. Participants are hospitalized adult patients with advanced cancer who are not receiving active anticancer treatment and who experience dyspnea at rest (Integrated Palliative Care Outcome Scale dyspnea score ≥2) despite continuous morphine infusion. Protocol treatment includes standardized morphine escalation plus continuous subcutaneous infusion of midazolam (9 or 6 mg/day for vulnerable patients) or placebo for 24 hours. The primary endpoint is feasibility, defined as completion of protocol treatment at 24 hours. Secondary endpoints include dyspnea intensity, anxiety, rescue morphine use, communication, adverse events, and 30-day survival. This feasibility trial will provide methodological insights and preliminary clinical data regarding midazolam as a second-line option for persistent dyspnea despite morphine infusion in patients with advanced cancer and help design future confirmatory trials.