In summary, the present study is the first time to compare the potential anti-tumor mechanisms of PZH and sorafenib in regulating the phosphorylation of enzymes related to cancer metabolic pathway by combining TMT and PRM mass spectrometry, and it was found that both PZH and sora could participate in regulating the phosphorylation of enzymes PGAM2, PFK1, ALDOA, and LDHA in metabolic related pathways, while sora and PZH have no effect on the phosphorylation of ACSL1 and ACSS2, respectively. Here, ACSS2 is linked to cancer.