OBJECTIVE： To observe clinical efficacy and safety of sertraline hydrochloride combined with esomeprazole in the treatment of patients with gastroesophageal reflux disease complicating with depression. METHODS： 80 patients with gastroesophageal reflux disease complicating with depression selected from our hospital were divided into control group and observation group according to random number table， with 40 cases in each group. Control group received Esomeprazole magnesium enteric-coated tablets orally 40 mg， qd； observation was additionally given Sertraline hydrochloride tablets 50 mg， qd， on the basis of control group. Both groups received treatment for 1 month. Clinical efficacies of 2 groups were observed as well as clinical symptom score， gastroesophageal reflux disease diagnostic questionnaire （GERD Q scale） score， SDS score. The occurrence of ADR was compared between 2 groups. RESULTS： The total effective rate of observation group 92.50％， which was significantly higher than 77.50％ of control group， with statistical significance （P＜0.05）. Before treatment， there was no statistical significance in clinical symptom score， GERD Q scale score and SDS score （P＞0.05）. After treatment， above scores of 2 groups were improved significantly， and the observation group was significantly better than the control group， with statistical significance （P＜0.05）. There was no statistical significance in the incidence of ADR between 2 groups （P＞0.05）. CONCLUSIONS： Sertraline hydrochloride combined with esomeprazole shows significantly therapeutic efficacy in the treatment of patients with gastroesophageal reflux disease complicating with depression， and can effectively alleviate the clinical symptoms and improve depression with good safety.