〔Abstract〕 Objective To investigate the effect of the expression of FASTKD4 in osteosarcoma and its effect on proliferation and apoptosis of osteosarcoma cells. Methods The levels of FASTKD4 mRNA were detected by qPCR,and protein was detected by immunohistochemistry in osteosarcoma and paracancerous tissues.The levels of FASTKD4 RNA were detected by qPCR in different osteosarcoma cells, and the osteosarcoma cell Saos-2 was used as the research object.Saos-2 cells were transfected with FASTKD4 small interfering RNA(shFASTKD4 group) and negative control(shCtrl group).qPCR and Western blot were used to detect the FASTKD4 mRNA and protein in transfected Saos-2 cells.The proliferation of transfected Saos-2 cells were detected by multiparametric high-content screening and CCK-8.The colony formation ability and apoptosis of transfected Saos-2 cells were detected by clone formation assay and flow cytometry. Reuslts The results of qPCR and immunohistochemistry showed the expression of the FASTKD4 in osteosarcoma tissues was higher than that in paracancerous tissues(P<0.05).The proliferation and colony formation ability of shFASTKD4 group were suppressed when compared with shCtrl group(P<0.05).The percentage of apoptosis in shFASTKD4 group was higher than that in shCtrl group(P<0.05). Conculsion This study confirmed that FASTKD4 was highly expressed in osteosarcoma tissues, and silencing of FASTKD4 could inhibit proliferation, colony formation of osteosarcoma cell and induce the apoptosis of osteosarcoma cell, We also found that FASTKD4 Knockdown inactivated PI3 K/AKT Signaling pathway in osteosarcoma cells.