Objective The aim of this study was to investigate the effects of general practice mode combined with duloxetine on psychological status， sleep quality and serum inflammatory cytokines in patients with Fibromyalgia Syndrome （FMS）. Methods A total of 105 FMS patients in Chengde Central Hospital from January 2019 to December 2021 were divided into the combined group （53 cases） and the control group （52 cases） by the random number table method. The two groups were treated with general practice mode combined with duloxetine or duloxetine alone. The single course of treatment lasted for 4 weeks. Their efficacy and safety were evaluated after 2 courses of intervention. Visual analogue scale （VAS）， Hamilton Anxiety assessment scale （HAMA）， Hamilton Depression Scale （HAMD） and Pittsburgh Sleep Quality Index （PSQI） were performed before and after treatment. The pain， psychological status and sleep quality of the patients were evaluated. Blood samples were taken to measure the serum levels of tumor necrosis factor?α （TNF?α）， interleukin?1 （IL?1） and IL?6 before and after treatment. Results The total effective rate in the study group was 96.23%， which was higher than that in the control group （82.69%， P < 0.05）. Compared with those before treatment， VAS， HAMA， HAMD and PSQI scores， serum TNF?α， IL?1 and IL-6 levels in the two groups were all decreased after treatment， and those in the study group were lower than those in the control group （P < 0.05）. There was no statistically significant difference in the incidence of adverse reactions between two groups （7.55% vs. 19.23%， P > 0.05）. Conclusion General practice mode combined with duloxetine was safe and effective in the treatment of FMS， which could significantly relieve anxiety and depression of patients， improve their sleep quality， and reduce the level of serum inflammatory cytokines.