Postoperative visceral pain is common after surgery and previous studies have demonstrated that oxycodone is an effective treatment. In this study, we compared the effects of preemptive oxycodone to equal dose of sufentanil on postoperative pain and serum level of inflammatory factors (TNF-α, IL-6, IL-10) after laparoscopic cholecystectomy. Forty patients undergoing laparoscopic cholecystectomy were randomized into preemptive oxycodone group or preemptive sufentanil group. Patients were given either oxycodone 0.1?mg/kg (oxycodone group, n?=?20) or sufentanil 0.1 μg/kg (sufentanil group, n?=?20) for preemptive analgesia. We evaluated pain/sedation scores at 0?h, 0.5?h, 2?h, 4?h, 6?h, 8?h and 24?h after surgery and measured serum concentrations of TNF-α, IL-6 and IL-10 before surgery and at 0?h, 6?h and 24?h after surgery. Twenty patients were recruited in each group. Numerical rating scale (NRS) of visceral pain in the oxycodone group at 2?h when resting (0.5(0,2.75) vs 3(2,4), P?=?0.008) and moving (0.5(0,3) vs 3(2.25,4), P?=?0.015) and 4?h when moving (2(0,3) vs 3(0,4.75), P?=?0.043) after surgery were significantly lower than the sufentanil group. Serum concentrations of TNF-α at 6?h (38.68?±?10.49 vs 73.02?±?16.27, P<0.001) and 24?h (43.12?±?8.40 vs 74.00?±?21.30, P<0.001) in the oxycodone group were lower than the sufentanil group. Preemptive oxycodone 0.1?mg/kg administration could effectively suppress visceral pain at 2?h and 4?h after surgery and had lower inflammatory marker, serum TNF-α, level when compared to equal dose of sufentanil. Clinical trials registration number: ChiCTR-IOR-17013738 http://www.chictr.org.cn/showproj.aspx?proj=17346 . Date of registration: 6th December 2017.