<i>In vivo</i>, KCNH2 knockdown significantly inhibited tumor growth.<h4>Conclusion</h4>This integrative AI-driven and multi-omics strategy identifies KCNH2 as a biologically relevant and translationally informative candidate target potentially linked to the anti-glioma effects of Acorus tatarinowii. Here, KCNH2 is linked to central nervous system cancer.