Objective To explore the changes of clinical symptoms and working memory in patients with depression before and after treatment in the acute phase and their correlation. Methods Patients with depression, who were admitted to the outpatient clinic of Beijing Anding Hospital affiliated to Capital Medical University from July 2017 to December 2019, were recruited, given 10-20 mg/d Escitalopram oxalate treatment per day, and followed up for 12 weeks. At baseline and the end of the 12th week, self-ordered pointing task (SOPT) and delayed recall task were used to evaluate working memory, and the HAMD-17 scale was used to evaluate clinical symptoms. Chi-square test, Wilcoxon rank sum test and Spearman correlation analysis were used to compare the changes of each index and the correlation between them. Results A total of 139 patients with depression were recruited, among which 73 patients completed 12 weeks follow-up. Anxiety symptoms are related to working memory accuracy under K2 load conditions (r=-0.171,P < 0.05) and are related to working memory capacity (r=-0.89,P< 0.05). At the end of the 12th week, 43 patients (58.9%) had a complete remission. There was a statistically significant difference in the decrease of HAMD-17 score between the remission group [16.00 (12.00,19.00)] and the non-remission group [8.00 (4.00,11.00)] (P< 0.05). There was statistically significant difference in the depressive symptoms [7.00(6.00,9.00) vs 5.00(3.00,5.00)], anxiety symptoms[4.00(3.00,6.00) vs 2.00 (1.00,4.00)], insomnia symptoms [1.00(0,3.00) vs 1.00(0,2.00)], and somatic symptoms [2.00(1.00,3.00) vs 1.00 (0,3.00)] between remission group and non-remission group (all P<0.05). After 12 weeks of follow-up, The total score of HAMD-17 and the change value of each dimension had no correlation with the change value of each dimension of working memory (P> 0.05). Conclusions Anxiety symptoms of patients with depression are related to working memory. There is no correlation between clinical symptoms and working memory changes before and after treatment in the acute phase.