Objective To investigate the effect of Duloxetine combined with non-steroidal anti-inflammatory drugs on pain and quality of life in patients with chronic osteoarthritis.Methods A total of 150 patients with chronic osteoarthritis treated in Xinyi People's Hospital from August 2022 to August 2023 were selected as the research objects,and they were divided into observation group(75 cases)and control group(75 cases)by random number table method.The control group was treated with non-steroidal anti-inflammatory drugs alone,and the observation group was treated with Duloxetine combined with non-steroidal anti-inflammatory drugs.The clinical efficacy,pain,mental state,quality of life and adverse reactions were compared between the two groups.Results After 8 weeks of treatment,the total effective rate of the observation group was higher than that of the control group,the difference was statistically significant (P＜0.05).After 8 weeks of treatment,visual analogue score(VAS),present pain intensity(PPI)and pain rating index(PRI)in observation group were lower than those in control group,and the differences were statistically significant (P＜0.05).After 8 weeks of treatment,the scores of Hamilton anxiety scale(HAMA)and Hamilton depression scale(HAMD)in the observation group were lower than those in the control group,and the differences were statistically significant (P＜0.05).After 8 weeks of treatment,the short form 36-item health survey(SF-36)scores in the observation group were higher than those in the control group,and the differences were statistically significant (P＜0.05).There was no significant difference in the total incidence of adverse reactions such as gastrointestinal discomfort,appetite loss,lethargy and sweating between the two groups after 8 weeks of treatment (P＞0.05).Conclusion Duloxetine combined with non-steroidal anti-inflammatory drugs is effective in the treatment of chronic osteoarthritis,which can effectively relieve pain,improve psychological state and quality of life,and have good safety.