Here, to capitalize on the link between PKM2 and serine biosynthesis pathway in NSCLC, we used the PKM2 inhibitor (PKM2-IN-1) and PHGDH inhibitor (NCT-503) to evaluate the anti-cancer effect and the mechanism of PKM2-IN-1 in combination with NCT-503 in A549 cells and a xenograft model. The gene discussed is PHGDH; the disease is non-small cell lung carcinoma.