This research was aimed at discussing the application value of different machine learning algorithms in the prediction of early Alzheimer's disease (AD), which was based on hippocampal volume changes in magnetic resonance imaging (MRI). In the research, the 84 cases in American Alzheimer's disease neuroimaging initiative (ADNI) database were selected as the research data. Based on the scoring results of cognitive function, all cases were divided into three groups, including cognitive function normal (normal group), early mild cognitive impairment (e-MCI group), and later mild cognitive impairment (l-MCI group) groups. Each group included 28 cases. The features of hippocampal volume changes in MRI images of the patients in different groups were extracted. The samples of training set and test set were established. Besides, the established support vector machine (SVM), decision tree (DT), and random forest (RF) prediction models were used to predict e-MCI. Metalinear regression was utilized to analyze MRI feature data, and the predictive accuracy, sensitivity, and specificity of different models were calculated. The result showed that the volumes of hippocampal left CA1, left CA2-3, left CA4-DG, left presubiculum, left tail, right CA2-3, right CA4-DG, right presubiculum, and right tail in e-MCI group were all smaller than those in normal group (P < 0.01). The corresponding volume of hippocampal subregions in l-MCI group was remarkably reduced compared with that in normal group (P < 0.001). The volumes of regions left CA1, left CA2-3, left CA4-DG, right CA2-3, right CA4-DG, and right presubiculum were all positively correlated with logical memory test-delay recall (LMT-DR) score (R2 = 0.1702, 0.3779, 0.1607, 0.1620, 0.0426, and 0.1309; P < 0.001). The predictive accuracy of training set sample by DT, SVM, and RF was 86.67%, 93.33%, and 98.33%, respectively. Based on the changes in the volumes of left CA4-DG, right CA2-3, and right CA4-DG, the predictive accuracy of e-MCI and l-MCI by RF model was both higher than those by DT model (P < 0.01). Besides, the predictive accuracy, sensitivity, and specificity of e-MCI by RF model was all notably higher than those by DT model (P < 0.01). The above results demonstrated that the effective early AD prediction models were established by the volume changes in hippocampal subregions, which was based on RF in the research. The establishment of early AD prediction models offered certain reference basis to the diagnosis and treatment of AD patients.