Objectives: Proinflammatory cytokine level in plasma and cerebrospinal fluid (CSF) is an indicator of inflammatory response following craniotomy. Lidocaine is local anesthetic that also has anti-inflammatory and neuroprotective effect. Primary aim of this trial is to determine the influence of lidocaine on the perioperative levels of pro-inflammatory cytokines interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in plasma and CSF in cerebral aneurysm patients. Secondary aim is incidence of major neurological and infectious complications, as well as treatment outcome in both groups. Patients and Methods: This prospective randomized study included 40 patients undergoing craniotomy and cerebral aneurysm clipping surgery. Patients were randomly assigned to the lidocaine or to the control group. Patients in lidocaine group, additional to general anesthesia, received topical anesthesia of the throat prior to endotracheal intubation and scalp block prior to Mayfield frame placement, both done with lidocaine. Patients in control group had no lidocaine administered. We measured concentrations of IL-1β, IL-6 and TNF-α in plasma and CSF, at specific timepoints perioperatively. We also did follow up on postoperative treatment course as well as outcome of included patients. Results: We found significantly higher plasma concentrations of IL-6 in patients in both groups, at timepoint 24 hours after begining of anesthesia. Concentrations of IL-6 and IL-1β in CSF were also significantly higher at the end of surgery compared to baseline values in control group. IL-6 levels in CSF of patients in lidocaine group at the end of surgery were significantly lower compared to those in control group. There were no significant differences in postoperative neurologic and infectious complications incidence between the groups, as well as in treatment outcome. Conclusion: Cerebral aneurysm surgery is followed by increase of proinflammatory cytokine levels in plasma and CSF. Lidocaine administration deminished increase of cytokine concentrations in CSF and this way might influence inflammatory response following craniotomy.