Abstract: Objective To observe the effect of oxycontin combined with flurbiprofen axetil in the treatment of bone metastasis pain from moderate to severe tumors. Methods Total 100 patients with moderate or severe tumors pain and bone metastasis (NRS ≥ 4) were divided into study group and control group according to random number table method, 50 patients in each group. The patients in the control group were given oxcontin analgesia, and the patients in the study group were given oxcontin combined with flurbiprofen axetil analgesia. The dosage, times of pain outbreak and adverse drug reactions were recorded, the level of serum stress-response factors were measured, and the analgesic effect was evaluated. Results The levels of serum E, NE and Cor in the study group[(37.28±4.85) ng/mL, (41.08±5.74) mg/mL, (12.05±1.96) μg/dL] were lower than those in the control group[(49.57±5.72) ng/mL, (66.63±6.55) mg/mL, (16.37±2.21) μg/dL)], all P<0.001. The total effective rate of pain relief in the study group (92.00%) was significantly higher than that in the control group (76.00%), χ²=4.762, P=0.029. The dosage of oxycontin[(407.59±52.61) mg] was significantly lower than that in the control group[(486.40±73.83) mg], and the number of outbreaks of pain in the study group (6.82±1.09) was significantly lower than that of the control group (12.74±2.31), t=-6.198, -15.776, all P<0.001. There was no significant difference in the overall incidence of adverse drug reactions (44.00% vs. 52.00%) between the two groups, χ²=0.641, P=0.432. Conclusion Oxycontin combined with flurbiprofen axetil can effectively alleviate the stress response of patients with moderate or severe bone metastasis pain, reduce the dosage of analgesic drugs, improve the analgesic effect level, and do not increase the adverse drug reactions.