Objective To investigate the effect of scalp nerve block (SNB) combined with dexmedeto- midine (Dex) injection on postoperative recovery quality in patients undergoing supratentorial tumor resection. Methods Based on factorial trail design, 160 patients who were scheduled for supratentorial tumor resection were randomly divided into four groups: control group (C group C), scalp nerve block group (SNB group), dexmedetomidine group (Dex group) and scalp nerve block combined with dexmedetomidine group (SNB+Dex group). Then, the 40-item Quality of Recovery Score (QoR40 score) was used to evaluate the recovery quality 1 day before operation (D0), and 1, 3 and 7 d after operation (D1, D3 and D7). The serum concentration of markers of nerve injury [S100β protein, glial fibrillary acid protein (GFAP) ] was detected right and 24 h after operation. The two groups were compared as well in terms of the score by the numerical rating scale (NRS) 24 h and 48 h after operation, frequency of analgesia, incidence of adverse events, use of vasoactive agents, incidence of coughing and agitation during extubation, nausea and vomiting (PONV) within 48 h after operation as well as the postoperative hospitalization stay. Results In D1 and D3, the interaction between SNB and Dex on total score of QoR-40 scale was significant (P < 0.05), but the interaction between the two factors was not significantly at D7 (P > 0.05), and their main effects were significant (P < 0.05). As for serum S100β and GFAP concentrations, the Dex main effect was significant at D1 (P < 0.05), and the SNB main effect and the two-factor interaction were not significant (P > 0.05). The incidence of intraoperative hypertension, tachycardia, utilization rate of vasoactive drugs, coughing and agitation during extubation in SNB+Dex group were significantly lower than those in C group (P < 0.05). The frequency of postoperative analgesic drugs in SNB group and SNB +Dex group was significantly lower than that in C group (P < 0.05). The postoperative NRS score at 48 h of the other three groups was significantly lower than that of C group (P < 0.05). There was no significant difference in the incidence of PONV and the length of hospitalization stay during 48 h after surgery (P > 0.05). Conclusion SNB combined with Dex injection can improve the early postoperative QoR-40 score in patients undergoing supratentorial tumor resection, reduce the serum concentration of nerve injury markers, reduce the incidence of perioperative adverse events, alleviate postoperative pain, lower the use of analgesic drugs and improve the early postoperative recovery. [ABSTRACT FROM AUTHOR]