Objective To discuss the effect of intravenous infusion of dexmedetomidine combined with lidocaine on inflammatory response in thoracoscopic radical resection for esophageal carcinoma under general anesthesia combined with paravertebral nerve block (PVB). Methods According to the random number table method, 100 patients who suffered from esophageal carcinoma and received thoracoscopic radical resection under general anesthesia combined with PVB in Gaozhou People's Hospital from August 2018 to August 2020 were enrolled. They were divided into four groups (n=25): a control group, a dexmedetomidine group, a lidocaine group and a combination group. All patients underwent PVB before induction of anesthesia. Then, 10 min before induction of anesthesia, the dexmedetomidine group and lidocaine group were intravenously infused with 0.5 μg/kg dexmedetomidine or 2% lidocaine hydrochloride at 1.5 mg/kg within 10 min, followed by a maintain dose of 0.4 μg·kg−1·h−1 or 1.5 mg·kg−1·h−1 30 min before the end of the operation. The combination group was infused with dexmedetomidine and 2% lidocaine hydrochloride 10 min before anesthesia induction at the same dosing methods mentioned above. The control group was intravenously infused with the same dose of normal saline. Their operation time, anesthesia time, recovery time, extubation time, propofol dosage and remifentanil dosage were recorded. Their levels of serum interleukin‑6 (IL‑6) and tumor necrosis factor (TNF‑α) were compared among the four groups before induction(T1), at the end of operation (T2), 2 h after surgery (T3) and 24 h after surgery (T4). The adverse reactions were recorded. Results There was no statistical difference in operation time and anesthesia time among the four groups (P>0.05). Compared with the control group and lidocaine group, the dexmedetomidine group and combination group showed remarkable increases in recovery time and extubation time, and decreases in the doses of propofol and remifentanil (P<0.05), where the changes in the combination group were more obvious (P<0.05). There was no statistical difference in the levels of serum IL‑6 and TNF‑α among the four groups at T1 (P>0.05). At T2‒T4, the levels of serum IL‑6 and TNF‑α in the four groups were all higher than those at T1 (P<0.05). At T3‒T4, the levels of serum TNF‑α in the lidocaine group were significantly lower than that in the control group (P<0.05). At T2‒T4, compared with the control group and the lidocaine group, the levels of serum IL‑6 and TNF‑α in the dexmedetomidine group and combination group substantially decreased (P<0.05), where the changes in the combination group were more obvious (P<0.05). No serious adverse reactions were reported in the four groups. Conclusions Intravenous infusion of dexmedetomidine combined with lidocaine significantly relieve the inflammatory response in esophageal carcinoma patients undergoing thoracoscopic radical resection under general anesthesia combined with PVB.