Following overexpression of the global regulator VeA, the antitumor activity of the crude extract from strain VeAOE was increased compared to WT. Multiple classes of antitumor active substances were screened by the metabolome, and 48 key genes that may be affiliated with antitumor activity were screened by combining database analysis of the transcriptome, revealing that the global regulator VeA mediates the antitumor activity of endophytic Fusarium solani.