Objective: To analyze the relationship between interleukin-6 (IL-6), glial fibrillary acidic protein (GFAP), calcium binding protein S100A8/A9 and functional prognosis of patients with sICH after the minimally invasive evacuation of hematoma and their predictive value. Methods: One hundred and eighteen patients with sICH in basal ganglia who underwent the minimally invasive evacuation of hematoma and hospitalized in our hospital from January 2016 to December 2018 were selected. According to the modified Rankin scale (mRS) 1 month after the onset, they were divided into a good prognosis group and a poor prognosis group, including 66 cases and 52 cases respectively. The levels of IL-6, GFAP and S100A8/A9 in serum were detected before and the next day after the minimally invasive evacuation of hematoma. And then the preoperative and postoperative levels of IL-6, GFAP and S100A8/A9 were compared between the two groups; the relationship between the above indicators and functional prognosis of patients was analyzed by Binary logistic regression analysis; the correlation between the above indexes and mRS score was analyzed by Spearman rank correlation analysis; the predictive value of the above indicators for the functional prognosis of sICH patients was analyzed by Receiver operating characteristic curve (ROC), and the AUC of each indicator was compared by Hanley & McNei test. Results: The preoperative serum levels of IL-6, GFAP and S100A8/A9 in patients of poor prognosis group had no significantly differences with those of good prognosis group (P>0.05). The postoperative serum levels of IL-6, GFAP and S100A8/A9 in patients of poor prognosis group were significantly higher than those of good prognosis group (P<0.05). Binary logistic regression analysis showed that the postoperative levels of IL-6, GFAP, S100A8/A9 were independent factors of influencing functional prognosis for patients (P<0.05). Spearman rank correlation analysis showed that the postoperative levels of IL-6, GFAP, S100A8/A9 were significantly and positively correlated with mRS score (P<0.05). ROC curve analysis showed that the AUC of postoperative levels of IL-6, GFAP, S100A8/A9 and their combined predictors in predicting the functional prognosis of sICH patients after minimally invasive evacuation of hematoma were 0.817, 0.770, 0.819 and 0.928, respectively (P<0.05), and the AUC, sensitivity (80.8%) and specificity (92.4%) of combined predictors for prediction were the highest. Conclusion: The levels of IL-6, GFAP and S100A8/A9 after minimally invasive evacuation of hematoma may affect the functional prognosis of sICH patients. The combination of postoperative IL-6, GFAP and S100A8/A9 can be used to predict the functional prognosis of sICH patients, which is worthy of clinical recommendation.