In this study, we proposed a cross-species, evidence-based gene ranking strategy and demonstrated it in the eight alcoholism or ethanol response related datasets from four species (human, mouse, fly, and worm). Through the use of permutation and FDR analyses, we evaluated 10 weighting score matrices and found that one of them had the best performance. Using this optimal weighting matrix, we selected 47 genes whose scores were greater than 2 for follow up bioinformatics analysis. Functional enrichment tests revealed that these 47 genes are involved in brain responses to ethanol and neural adaptations occurring with alcoholism. Our results, with further experimental validation in three animal models, suggest that our approach is useful for cross-species gene prioritization.