Objective To explore the effects of patient‑controlled epidural analgesia (PCEA) and patient‑controlled intravenous analgesia (PCIA) on postoperative analgesia and cytokine levels in serum on patients undergoing resection of esophageal carcinoma. Methods Thirty⁃six patients scheduled for elective resection of esophageal carcinoma were assigned to PECA group (21 cases) or PCIA group (15cases) according to the random number table method in a 3:2 ratio. Based on the same other anesthetics in the two groups, the patients in the PCEA group received combined use of ropivacaine (0.15%) and fentanyl (2 mg/L) for PCEA, while the patients in the PCIA group used fentanyl (12 μg/kg) for PCIA as an analgesic regimen. The general information of patients in both groups, postoperative Numerical Rating Scale (NRS) scores at 2, 4, 8, 16, 24, 36 h and 48 h for rest and movement, and the occurrence of postoperative adverse events were recorded. The serum levels of interleukin (IL)⁃1β, IL⁃6, IL⁃10, and tumor necrosis factor⁃α (TNF⁃α) at preoperative, end of the surgery, 24 h and 48 h after the surgery were measured in both groups. Results There were no statistically significant differences in general patient information between the two groups (all P>0.05). The NRS scores at rest and during movement in the PCEA group were lower than those in the PCIA group at 4, 8, 16, 24 h and 36 h after surgery (all P<0.05). However, there was no statistically significant difference in NRS scores at rest and during movement between the two groups at 2 h and 48 h after surgery (all P>0.05). There were no statistically significant differences in the incidence of adverse events between the two groups (all P>0.05). Serum IL‑6 levels in the PCEA group were lower than those in the PCIA group at 48 h postoperatively (P<0.05). In addition, the serum levels of IL⁃1β, IL⁃6, and IL⁃10 in the PCEA group at 48 h after surgery were lower than the levels at 24 h after surgery (all P<0.05). There was no statistically significant difference between the two groups for the remaining indicators (all P>0.05). Conclusions Epidural analgesia was superior to intravenous analgesia for patient‑controlled postoperative pain relief after esophagectomy and reduced serum IL‑6 levels at 48 h after surgery.