The present study aimed to investigate the effect of cytochrome P450 3A4 (CYP3A4)*18B polymorphisms and the interaction of the µ opioid receptor gene (OPRM1) A118G and CYP3A4*18B polymorphisms on postoperative fentanyl analgesia in Chinese Han patients undergoing radical gastrectomy. In total, 97 patients scheduled to undergo radical gastrectomy under general anesthesia were enrolled in this study. Post‑operative patient‑controlled intravenous analgesia of fentanyl was administered as analgesia up to 48 h following surgery. Venous blood (2 ml) was obtained from each patient to measure the OPRM1 A118G and CYP3A4*18B genotypes. The differences in fentanyl consumption and adverse effects were compared among the genotypes at 24 and 48 h following surgery. In the first 48 h following surgery, patients in the CYP3A4*18B/*18B group consumed significantly less fentanyl compared with patients in the *1/*1 group (P=0.032). With regards to the joint genetic effect, during the 48‑h period, patients with AA and *1*18B polymorphisms received fewer fentanyl doses compared with those with AG and *1*1 (P=0.049), while patients with AG and *1*18B polymorphisms received significantly fewer fentanyl doses compared with those with AG and *1*1 (P=0.010), and patients with *18B*18B polymorphisms received significantly fewer fentanyl doses compared with those with AA and *1*1 (P=0.024) or those with AG and *1*1 polymorphisms (P=0.006). No correlation between OPRM1 A118G and CYP3A4*18B and postoperative nausea, vomiting and dizziness was found. Results demonstrated that 48 h following surgery, patients with the CYP3A4*18B/*18B genotype required less fentanyl than patients with the CYP3A4*1/*1 genotype to control pain. Additionally, the combined genotype of CYP3A4*18B and OPRM1 A118G may affect fentanyl doses administered for pain control, but not postoperative nausea, vomiting and dizziness.