The study was aimed to investigate the pathogens distribution and risk factors for PICC-related bloodstream infection in intensive care unit (ICU) patients. 402 patients placed with PICC in ICU were recruited in the study. The microbiological characteristics of PICC-related infection were investigated by Vitek 2 Compact automated microbial system. Antibiotics sensitivity was performed with disk diffusion and minimum inhibitory concentration (MIC) methods. Multivariate logistic and cox analyses were performed to identify the risk factors for PICC-related infection in ICU patients. 38 PICC-related infection cases were observed, and its morbidity was 9.45%. The morbidity was significantly higher in power PICC cases than that in common PICC cases. Gram-positive bacteria might be responsible for the major infection cases, followed by gram-negative bacteria, and fungi. Drug sensitivity analyses indicated that gram-negative bacteria showed low resistance to carbapenems antibiotics, and Cefperazone/sulbactam. The gram-positive bacterial exhibited sensitive to Teicoplanin and Vancomycin. The isolated fungi showed low resistance to the commonly used antifungal antibiotics. Multivariate analyses demonstrated that power PICC, high Charison scores, diabetes mellitus, double lumens triple lumens were risk factors for PICC-related infections among ICU patients. Power PICC, high Charison scores, diabetes mellitus, multi-lumens are risk factors for PICC-related bloodstream infection in ICU patients.