Background & aims: Nutritional support for patients in the intensive-care unit (ICU) is a part of standard care which promotes medical quality and decreases nosocomial infection. Supplemental parenteral nutrition (SPN) approach (enteral nutrition (EN) combined with parenteral nutrition (PN) when EN alone is insufficient) has become one major concern in nutrition research field. This research aims to explore the following relationships: (i) the relationship between SPN and nosocomial infection, (ii) the relationship between early and late SPN initiation and the development of nosocomial infection. Methods: A retrospective study was conducted in patients who met the inclusion criteria from February 2012 to February 2015 in Pediatric ICU (PICU). Patients were classified into two groups according to nutrition delivery approach-SPN group and EN alone group. Then SPN group were further divided into two subgroups by initiation timing, which were defined as early-initiation SPN and late-initiation SPN group respectively. Age, gender, serum albumin at admission, severity of disease, length of stay in PICU, nutrition delivery approach, amounts of delivered caloric intake and occurence of nosocomial infection were recorded. Univariate analysis and binary logistic regression analysis were performed to identify the risk factors and assess the independent effect of SPN approach on nosocomial infection in PICU of Emergency Department. Results: 204 patients were included in our study. Compared with EN alone group, patients delivered by SPN approach had a higher nosocomial infection rate (34.0 vs. 10.9 %, p < 0.001). The late-initiation subgroup of SPN approach was found to be an independent predictor of nosocomial infection in the logistic regression analysis model (OR = 3.40; 95 % CI, 1.13 similar to 10.19; p = 0.029). Serum albumin at admission (OR = 0.91; 95 % CI, 0.84 similar to 0.97; p = 0.008), mechanical ventilation (OR = 3.85; 95 % CI, 1.43 similar to 10.39; p = 0.008), severity of disease (OR = 3.79; 95 % CI, 1.03 similar to 13.99; p = 0.045) and PICU length of stay (OR = 1.23; 95 % CI, 1.11 similar to 1.35; p < 0.001) were also identified as significant risk factors for nosocomial infection. Conclusions: Our study shows late-initiation SPN approach increases the incidence of nosocomial infection compared with early-initiation approach in critically ill children in PICU of Emergency Department. Compared with EN alone group, patients delivered by SPN approach had a higher nosocomial infection rate.