Objective To investigate the dynamic changes and causes of psychological distress in postoperative patients with gastric cancer during chemotherapy, and to provide reference for alleviating their negative emotions. Methods A longitudinal survey was conducted on the day before chemotherapy (T1) and at the firstcycle (T2), thirdcycle (T3), and sixthcycle (T4) of chemotherapy by using a sociodemographic questionnaire, the Distress Thermometer, and the Hospital Anxiety and Depression Scale (HADS). Results A total of 212 patients completed the study. The incidence rates of moderate to severe psychological distress were 62.74%, 70.28%, 47.17%, and 31.60% at the 4 timepoints, respectively. Significant differences were found in psychological distress score, anxiety and depression scores among 4 timepoints (P<0.01 for all). The psychological distress score was the highest at T2 (4.84±1.27) and the lowest at T4 (2.67±1.23). Multivariate stepwise regression analysis indicated that gender, age, education, and anxiety were influencing factors of psychological distress at 4 timepoints; depression was an influencing factor at T1, T3 and T4; personal monthly income was an affecting factor at T1 and T3;and tumor staging was a predictor at T1 （adjusted R2 being 0.836，0.512，0.683，and 0.605 at 4 timepoints；P<0.05，P<0.01）. Conclusion Psychological distress was common in patients with gastric cancer during postoperative chemotherapy, and it is dynamically changed. Targeted interventions should be taken, especially for those who are female, advanced aged, anxious and depressed, and those who have low education and monthly income, to alleviate psychological distress of patients and help them complete the chemotherapy and improve quality of life.