<p>Little is still known about the risk factors for skin pressure injury (SPI) in neonatal patients with peripherally inserted central catheter (PICC). The aim of this study was to investigate the effect of clinical factors on the risk of PICC-related SPI. The medical records of PICC neonatal patients attending our paediatric department from January 2020 to January 2023 were retrospectively analyzed. The patients were divided into the SPI group and the non-SPI group according to whether or not the SPI occurred during the timeframe of when the PICC was in situ. The general data and laboratory indicators of the two groups were recorded and compared. Through univariate analysis and multivariate logistic regression, the link between factors and the presence or absence of PICC-related SPI was identified. A total of 244 neonatal patients with PICC with a mean age of 13.8 days were included in the study. The incidence of SPI was 10.4% (23/244). After univariate and multivariate logistic regression analysis, it was concluded that skin condition, delayed catheter maintenance cycle, and type of fluid infused were factors influencing the occurrence of SPI in patients with PICC (<i>p</i> &lt; 0.05). Skin condition, delay of catheter maintenance cycle, and type of fluid infused are independent risk factors for PICC-related SPI in neonatal patients. Healthcare workers and parents or carers need to work together to focus on PICC neonatal patients with the above risk factors to try to avoid SPI.</p>