Mandibular resection during maxillofacial cancer surgery evokes a strong sympathetic response requiring high doses of opioids. We studied the effect of the inferior alveolar nerve block (IANB) for analgesia in maxillofacial cancer surgeries. This randomised controlled study was conducted over five months in a tertiary care cancer hospital following Institutional Ethics approval and trial registration. Fifty consenting adult patients belonging to the American Society of Anesthesiologists (ASA) physical status I and II requiring maxillofacial cancer surgery with unilateral mandibular resection were recruited. Twenty-five patients in the study arm received ipsilateral IANB; a mock injection was given to the control group. Fentanyl requirement and haemodynamic parameters during primary tumour excision were the primary and secondary endpoints. Student's t-test was applied to compare primary and secondary endpoints. Forty-nine patients completed the study. Both arms were comparable with respect to age, gender distribution, ASA physical status and baseline heart rate (HR) and blood pressure (BP). The mean (standard deviation) intravenous fentanyl requirement during primary tumour excision in the IANB arm was 70(32) µg, significantly lower than 183(48) µg in the control arm, P < 0.001. The mean maximum HR during primary tumour excision was 82 and 99 per minute in the IANB and control arms, respectively (P < 0.001) whereas the maximum mean BP was 88 and 101 mm Hg, respectively (P < 0.001). IANB significantly reduced intraoperative fentanyl requirement and caused fewer haemodynamic changes during maxillofacial cancer surgery requiring unilateral mandibular excision.