Objective To evaluate the risk factors for catheter-related bloodstream infection (CRBSI) in very low birth weight infants (VLBWIs) receiving peripherally inserted central venous catheter (PICC). Methods VLBWIs who received PICC in neonatal intensive care unit (NICU) in the Third Affiliated Hospital of Zhengzhou University from January 2019 to November 2021 were selected. Clinical data of VLBWIs were analyzed retrospectively, case-control study was adopted, neonates with CRBSI were as case group and those without CRBSI were as control group, risk factors for CRBSI were analyzed by univariate and logistic regression. Results A total of 61 VLBWIs receiving PICC developed CRBSI, the total catheterization time was 26 521 days, incidence of CRBSI was 2.3 ‰. The main pathogens of CRBSI in VLBWIs were Staphylococcus epidermidis (23.0%), Klebsiella pneumoniae (19.7%) and Serratia marcescens (14.8%). Logistic regression analysis showed that birth weight < 1 000 g (OR=2.254), mechanical ventilation (OR=2.168), catheterization time ≤7 days (OR=2.534), PICC indwelling time≥21 days (OR=2.200) were independent risk factors for CRBSI in VLBWIs, and one-time puncture success (OR=0.378) was protective factor. Conclusion For VLBWIs, especially those with extremely low birth weight < 1 000 g, early postnatal catheterization and repeated puncture during catheterization should be avoided as much as possible, the indwelling time of PICC and mechanical ventilation time should be shortened as much as possible, which is of great significance for the prevention of CRBSI.