This study was designed to discuss the clinical effects of dexmedetomidine combined with oxycodone patient-controlled intravenous analgesia for patients with laparoscopic radical resection of rectal cancer. A total of 90 patients with rectal cancer undergoing laparoscopic radical resection surgery were selected. The patients were divided into A, B and C group using a random number table method, 30 cases in each group. Patients in group A received oxycodone (O) alone postoperatively; patients in group B received dexmedetomidine combined with oxycodone (DO) postoperatively; and patients in group C received dexmedetomidine (D) alone postoperatively. The Visual Analog Scale (VAS) score and Ramsay sedative score at 2h, 6h, 24h and 48h after surgery were evaluated, and the effective compressions number of controlled intravenous analgesia (CIA) was recorded. The occurrence of side effects including fever, nausea, vomiting, drowsiness, dizziness, itchy skin, respiratory depression and other adverse reactions were noted. CRP, TNF-α, and IL-6 were detected by ELISA prior to surgery and on the morning of the 1st and the 3rd day after surgery, respectively. VAS scores in group B were lower than group A and C, the effective compressions number of CIA in group B was less than group A and C, the incidence of adverse reactions in group B was lower than group A and group C. The levels of CRP, TNF-α and IL-6 at 72h after surgery in group B were lower than group A and C. Dexmedetomidine combined with oxycodone has better sedative and analgesic effects with less adverse reactions, it can reduce the release of inflammatory cytokines of CRP, TNF-α and IL-6 in the body and has certain clinical application value.