Background: Approximately 55-87% of the patients undergoing craniotomy experience moderate to severe pain during the first 48 hrs after surgery, which negatively influences patient's postoperative rehabilitation. Recently, local infiltration of analgesia (LIA) has been widely performed clinically as a promising analgesic method that could avoid the side effects of analgesics but only has a short pain-free duration; researchers have clarified that the addition of dexamethasone to LIA could provide significant analgesic effects and significantly prolong the duration of analgesic effects without obvious complications for various types of surgeries. To date, no studies have evaluated the addition of dexamethasone to LIA for patients receiving craniotomy. The aim of the study was to test the hypothesis that pre-emptive scalp infiltration with a steroid (dexamethasone) plus a local anesthetic (ropivacaine) could achieve superior postoperative analgesic effects to a local anesthetic (ropivacaine) alone in adult patients undergoing a craniotomy. Study design and methods: This study is a randomized controlled trial that will include one intervention and one control group involving a total of 140 adults scheduled for elective craniotomy for resection of supratentorial tumors under general anesthesia and with an anticipated full recovery within 2 hrs postoperatively. The intervention will involve preemptive scalp infiltration with ropivacaine plus dexamethasone (the dexamethasone group) or ropivacaine alone (the control group), and the participants in both groups will complete a 6-month follow-up. The primary outcome will be the cumulative sufentanil consumption within 48 hrs postoperatively. Discussion: The intervention, if effective, this study will provide clinically important information on the role of dexamethasone in scalp infiltration for post-craniotomy pain management.