Objective To investigate the effect of dexmedetomidine (Dex) or epidural blockade combined with general anesthesia on perioperative inflammatory cytokines in lung cancer patients undergoing video‑assisted thoracoscopic surgery. Methods Ninety lung cancer patients [American Society of Anesthesiologists (ASA) Ⅰ‒Ⅲ, age<70 years] undergoing video‑assisted thoracoscopic surgery were divided into three groups according to a random number table: a general anesthesia group (group G), an epidural blockade combined with general anesthesia group (group GE) and a Dex combined with general anesthesia group (group GD), with 30 patients in each group. Patients in group GE underwent epidural catheterization at T7-T8 before anesthesia induction, while groups G and GD was given normal saline or 1 μg/kg Dex via an intravenous infusion pump over 10 min after anesthesia induction. Before induction (T0), at the end of surgery (T1), and 24 h after surgery postoperatively (T3), blood samples from the right internal jugular vein were taken to measure the levels of interleukins (IL‑1β, IL‑6, and IL‑10) and tumor necrosis factor‑α (TNF‑α) by a double antibody sandwich ABC-ELISA method. The scores of Prince-Henry Pain Scale were evaluated 2 h after surgery (T2) and T3. The incidences of intraoperative hypotension, bradycardia and postoperative nausea and vomiting were recorded. Results Compared with those at T0, there were significant increases in the levels of IL‑1β, IL‑6, and TNF‑α and sharp decreases in the levels of IL‑10 at T1 and T3 in all groups (P<0.05). Compared with those in group G, the levels of IL‑1β and IL‑6 reduced in groups GD and GE at T1 and T3 (P<0.05), while the level of IL‑10 increased (P<0.05). At T1, the levels of TNF‑α in groups GD and GE decreased compared with those in group G (P<0.05). At T3, the level of TNF‑α in group GE was lower than that in group G (P<0.05), and there was no difference in TNF‑α between groups GD and GE (P>0.05). The scores of Prince-Henry Pain Scale in group GE were lower than those in other two groups (P<0.05). The incidence of nausea in groups GD and GE was significant lower than that in group G (P<0.05). Conclusions For lung cancer patients undergoing video‑assisted thoracoscopic surgery under general anesthesia, a combined use of 1 μg/kg Dex can significantly relieve inflammatory response, to an extent comparable to epidural blockade combined with general anesthesia.