Background. Peripherally inserted central catheter (PICC) is the most commonly used infusion route for chemotherapy in Chinese breast cancer patients because of its convenience, ease of operation, and many maintenance sites. Objective. The objective of this study is to investigate the effect of the first dressing change time on the healing of puncture site and the economic and psychological impact in patients with breast cancer after PICC insertion. Methods. From April 2020 to October 2020, 120 patients with PICC intubation after breast cancer surgery were selected as the research objects and divided into test group and the control group with 60 cases in each group according to the random number table method. The time of the first dressing change in the control group was routinely performed within 24 hours after PICC catheter placement, while the first dressing change in test group was performed at 48 hours after catheter placement. The effect of the first dressing change time after PICC catheterization on patients after breast cancer surgery was compared between the two groups. Results. There were significant differences between the two groups in the degree of pain after the first dressing change, the degree of oozing at the puncture site within 1 week, the duration of oozing, and the frequency of maintenance within 3 weeks, cost, depression, and anxiety ( P < 0.05 ). Conclusion. The first dressing change 48 hours after PICC cauterization in patients after breast cancer surgery reduces significantly puncture site bleeding, reduces the frequency of dressing change, and benefits the physical and mental health of patients.