Resistance to anoikis is a hallmark of human malignancies. Our results showed that hepatoma cells resisted anoikis by non-proliferation, non-apoptosis and cell cycle arrest which were termed synoikis-like. These synoikis-like cells are more resistant to extracellular stimuli and could spontaneously attach and proliferate again under suitable conditions, which indicate a reversible property of these cells. Microarray expression profile reveals the change of molecules involved in the synoikis-like hepatoma cells and our data indicated that ANGPTL4 contributed to anoikis resistance of hepatoma cells. These results demonstrated that hepatoma cells might resist anoikis through a synoikis-like survival style, which may facilitate tumor metastasis.