Aim: The aim of this study was to explore factors related to neurological deterioration (ND) after spontaneous intracerebral hemorrhage (sICH) and establish a prediction model based on random forest analysis in evaluating the risk of ND. Methods: The clinical data of 411 patients with acute sICH at the Affiliated Hospital of Jining Medical University and Xuanwu Hospital of Capital Medical University between January 2018 and December 2020 were collected. After adjusting for variables, multivariate logistic regression was performed to investigate the factors related to the ND in patients with acute ICH. Then, based on the related factors in the multivariate logistic regression and four variables that have been identified as contributing to ND in the literature, we established a random forest model. The receiver operating characteristic curve was used to evaluate the prediction performance of this model. Results: The result of multivariate logistic regression analysis indicated that time of onset to the emergency department (ED), baseline hematoma volume, serum sodium, and serum calcium were independently associated with the risk of ND. Simultaneously, the random forest model was developed and included eight predictors: serum calcium, time of onset to ED, serum sodium, baseline hematoma volume, systolic blood pressure change in 24 h, age, intraventricular hemorrhage expansion, and gender. The area under the curve value of the prediction model reached 0.795 in the training set and 0.713 in the testing set, which suggested the good predicting performance of the model. Conclusion: Some factors related to the risk of ND were explored. Additionally, a prediction model for ND of acute sICH patients was developed based on random forest analysis, and the developed model may have a good predictive value through the internal validation.