Abstract: Objective To detect the level of interleukin-6 (IL-6) in umbilical cord blood and evaluate its use in the diagnosis of premature infants with early-onset septicemia. Methods A total of 39 premature infants who were diagnosed with early-onset septicemia in Maternal and Child Healthcare Hospital of Shunyi District, Beijing from January 2017 to January 2018 were selected as a septicemia group. Meanwhile, another 53 non- septicemia premature infants who were admitted during the same period were select as a non- septicemia group. Their clinical data were collected. The levels of IL-6 in umbilical cord blood and peripheral blood were measured by ELISA. The ROC curves of umbilical cord blood and peripheral blood IL-6 in the diagnosis of septicemia were spotted. Results Compared with the non- septicemia group, the septicemia group presented decreased birth weight and shortened time of premature rupture of membranes, with increased incidences of less eating, less crying, less movement, abdominal distention and skin blossom (P<0.05). The levels of lactate, total bilirubin, C-reactive protein, and IL-6 in umbilical cord blood and peripheral blood were significantly higher in the septicemia group than those in the non-septicemia group (P<0.05). The ROC curve showed that the AUC of IL-6 in umbilical cord blood was 0.757, 95% CI (0.651-0.863), where the threshold value was 17.6 ng/L, the sensitivity was 56.4%, and the specificity was 94.3%. The AUC of IL-6 in peripheral blood was 0.768, 95% CI (0.665-0.871), where the threshold was 2.05 ng/L, the sensitivity was 69.2%, and the specificity was 83.0%. Conclusions The level of IL-6 in umbilical cord blood significantly increases on the early stage of septicemia, which may have clinical significance in the diagnosis of premature infants with early-onset septicemia.