This study aimed to establish an artificial neural network (ANN) model based on prostate cancer signature genes (PCaSGs) to predict the patients with prostate cancer (PCa). In the present study, 270 differentially expressed genes (DEGs) were identified between PCa and normal prostate (NP) groups by differential gene expression analysis. Next, we performed Metascape gene annotation, pathway and process enrichment analysis, and PPI enrichment analysis on all 270 DEGs. Then, we identified and screened out 30 PCaSGs based on the random forest analysis and constructed an ANN model based on the gene score matrix consisting of 30 PCaSGs. Lastly, analysis of microarray dataset GSE46602 showed that the accuracy of this model for predicating PCa and NP samples was 88.9 and 78.6%, respectively. Our results suggested that the ANN model based on PCaSGs can be used for effectively predicting the patients with PCa and will be helpful for early PCa diagnosis and treatment.