Abstract: Objective To evaluate the predictive values of serum vitamin D and hyaluronic acid（HA） levels for clinical prognosis of patients with short bowel syndrome（SBS）. Methods A total of 100 patients with SBS were recruited into the SBS group, and 100 healthy controls for physical examination during the same period were assigned into the control group. SBS patients received nutritional therapy, intestinal rehabilitation, and surgical treatment and followed up for one year to observe clinical prognosis. All SBS patients were classified into the good prognosis and poor prognosis groups. The serum 25-hydroxyvitamin D₃ （25（OH）D₃） and HA levels were compared between the SBS and control groups. The serum 25（OH）D₃, HA levels and other potential risk factors of 1-year prognosis were statistically compared between the good and poor prognosis groups. The 1-year prognostic factors of SBS patients were identified by logistic regression analysis. The receiver operating characteristic （ROC） curve was delineated to analyze the predictive values of serum 25（OH）D₃, HA alone and two combined for 1 year prognosis of SBS. Results The serum 25（OH）D₃ level in the SBS group was significantly lower, whereas the HA level was remarkably higher than those in the control group （both P < 0.05）. In the poor prognosis group, the composition ratio of residual small intestine length of ≤60 cm and the serum HA level were significantly higher, whereas the serum 25（OH）D₃ level was considerably lower than those in the good prognosis group （all P < 0.05）. Logistic regression showed that all these parameters were the risk factors affecting the 1-year prognosis of SBS patients （all P < 0.05）. The ROC curve results demonstrated that the optimal cut-off values of serum 25（OH）D₃ and HA levels for predicting poor prognosis of SBS patients were 15.74 μg/L and 235.70 μg/L. The area under the curve （AUC） predicted by serum 25（OH）D₃ and HA levels alone and two combined were 0.825, 0.763, and 0.855, respectively. The predictive value of the combination of the two is higher than that of the serum hyaluronic acid test alone（P < 0.05）. Conclusions In SBS patients, serum 25（OH）D₃ level is abnormally decreased, whereas serum HA level is abnormally increased. The combined detection of the two is more valuable than the detection of serum hualuronic acid in predicting the prognosis of SBS patients.