Objective To study the clinical therapeutic effect of paroxetine hydrochloride on refractory irritable bowel syndrome. Methods 124 patients with refractory irritable bowel syndrome , were randomly divided into conventional group (62 cases,receiving oral trimebutine maleate 0.1 g, 3/d and bifidobacteria capsules 420 mg, 3/d) and paroxetine group (62 cases, in addition to conventional treatment, oral paroxetine hydrochloride 20 mg, 1/d ).The course of treatment was 4 weeks for both groups.Before and after treatment , the Self-rating Anxiety Scale (SAS) and the Self-rating Depression Scale (SDS) were used for assessment.Symptom improvement and efficiency in the two groups after treatment were observed. Results In the paroxetine group, the total effective rate was 96.77% and 77.42% in the conventional group, with a significant difference(P<0.01) between the two groups. The SAS and SDS scores after and before treatment in the paroxetine groups were significantly different (P<0.01), SAS and SDS scores were not significantly different (P>0.05) in the conventional group before and after treatment.The SAS and SDS scores before treatment were significantly different between patients with irritable bowel syndrome and normal group (P<0.01).Conclusions Paroxetine hydrochloride in treatment of refractory irritable bowel syndrome is significantly efficient and can improve the patient's emotional state.