Abstract: OBJECTIVE To evaluate the efficacy and safety of paroxetine and other selective 5-HT reuptake inhibitors. METHODS Cochrane Library, web of science, CNKI, VIP, Wanfang Digital Journal Database were retridved. Systematic review(SR) and meta-analysis or randomized controlled trial(RCT) compared paroxetine with other selective 5-HT reuptake inhibitor efficacy and safety. Methodological quality evaluation and meta-analysis of included RCTs, referenced to SR and meta analysis conclusions. RESULTS A total of 15 RCTs were included in the comparison of efficacy and safety of paroxetine with other selective 5-HT reuptake inhibitors. The total effective rate of antidepression in the 2 groups was statistically significant (OR=1.45, 95%CI=1.01-2.09, P=0.04); the difference in HAMD scores after 2 weeks and 6 weeks of treatment was statistically significant(MD=-2.04, 95%CI=-2.59- -1.49, P<0.000 1; MD=-0.69, 95%CI=-1.18- -0.21, P=0.005); the difference in adverse reation after 6 weeks of treatment was statistically significant(OR=0.88, 95%CI=0.78-0.99, P=0.04). CONCLUSION Compared with other selective 5-HT reuptake inhibitors, paroxetine has lower total effective rate and onset rate, and higher incidence of adverse reactions, which is no longer recommended as first-line antidepressant.