The incidence of peripherally inserted central catheter (PICC)-related complications is higher in cancer patients than in noncancer patients. However, the pattern of specific complication occurrence over time remains unclear. The purpose of this study was to investigate the clinical characteristics of PICC-related complications in cancer patients undergoing chemotherapy.This prospective, observational study was conducted at a university-affiliated hospital in Western China. Cancer patients undergoing PICC insertion for anticancer treatment were recruited and followed up until the first week after catheter removal. Any complications, including occurrence time and outcomes, were recorded. The trajectory of specific PICC-related complications over time were identify based on the Kaplan‒Meier curve analysis.Of the 233 patients analyzed, nearly half (n = 112/233, 48.1%) developed 150 PICC-related complication events. The most common were symptomatic catheter-related thrombosis (CRT) (n = 37/233, 15.9%), medical adhesive-related skin injury (MARSI) (n = 27/233, 11.6%), and catheter dislodgement (n = 17/233, 7.3%), accounting for 54.0% (n = 81/150, 54.0%) of total complications events. According to Kaplan‒Meier curve analysis, symptomatic CRT, pain, phlebitis, and insertion site bleeding were classified as the "early onset" group mainly occurring within the first month post-insertion. Catheter fracture and catheter-related bloodstream infection were classified as the "late onset" group occurring after the second month post-insertion. MARSI, catheter dislodgement, occlusion, and insertion site infection were classified as the "persistent onset" group persistently occurring during the whole catheter-dwelling period. Among the 112 patients with PICC-related complications, 50 (44.6%) patients had their catheters removed due to complications, and 62 (55.4%) patients successfully retained their catheters until treatment completion through conventional interventions. The major reasons for unplanned catheter removal were catheter dislodgement (n = 12/233, 5.2%), symptomatic CRT (n = 10/233, 4.3%), and MARSI (n = 7/233, 3.0%), accounting for 58.0% (n = 29/50, 58.0%) of the total unplanned catheter removal cases. Catheter dwelling times between patients with complications under successful interventions (130.5 ± 32.1 days) and patients with no complications (138.2 ± 46.4 days) were not significantly different (t = 1.306, p = 0.194; log-rank test = 2.610, p = 0.106).PICC-related complications were pretty common in cancer patients undergoing chemotherapy. The time distribution of PICC-related complications varied, and medical staff should develop time-specific protocols for prevention. Because more than half of the patients with PICC-related complications could be managed with conventional interventions, PICCs remain a priority for cancer patients undergoing short-term chemotherapy. The study was registered in 02/08/2019 at Chinese Clinical Trial Registry (registration number: ChiCTR1900024890).© 2023. BioMed Central Ltd., part of Springer Nature.