Peripheral venous blood markers may reflect the systematic inflammatory response condition. Various indices have been used to evaluate Inflammatory Bowel Disease (IBD), however, there is no ideal maker to assess the IBD activity and severity. We aim to investigate the potential value of Systemic Inflammation Response Index (SIRI) in IBD patients, and use it to predict the disease activity and severity. We designed a retrospective study to evaluate the SIRI in estimating disease severity in patients with IBD. We enrolled 210 patients with IBD, included 110 cases of Ulcerative Colitis (UC) and 100 cases of Crohn’s Disease (CD) in our hospital, between May 2011 and October 2014. The blood samples were collected from the IBD patients before any treatment of antibiotics, steroids and surgery. The categorical variables were provided with frequencies and percentages (%), and using the Chi-square test. The univariate and multivariate logistic regression model analysis were used to determine the demographic and clinicopathological features with active IBD. The optimal cut-off value of SIRI by Receiver Operating Characteristic curve (ROC) was 0.86 × 109/L, and patients were stratified into 2 groups: a low SIRI group (SIRI<0.86 × 109/L) and a high SIRI group (SIRI ≥ 0.86 × 109/L). A high SIRI was significantly correlated with active IBD (P=0.019), CRP (P=0.002), ESR (P<0.001), NLR (P<0.001) and MLR (P<0.001). The active IBD was statistically significant between the two groups (P=0.019). Compared with the inactive IBD, the mild active and moderate active IBD were not statistically significant (P=0.907, 0.137), however, the severe active IBD was statistically significant (P<0.001). There was statistically significant of the different severity of active IBD between low SIRI group and high SIRI group (P=0.003). Multivariate analysis indicated that the CRP, ESR and SIRI were independently associated with active IBD. SIRI is cost-effective and convenient indicator in IBD patients and may be a new promising marker of the disease severity in IBD. High SIRI may help the doctors to make decisions for patients with active IBD.