The major findings include: (1) Decreased PGC1α and ID1 levels were observed in human lung primary and metastatic tumor specimens and were closely associated with a poor prognosis; (2) the suppression of PGC1α and ID1 promoted tumor growth, tumor-initiating potential, and bone metastasis through EMT in lung cancer; (3) the interaction between TCF4 and TWIST1, which is inhibited by ID1, was responsible for PGC1α loss-induced EMT. Here, TCF4 is linked to lung cancer.