In summary, our current study reveals that the knockdown of KCNQ1OT1 inhibits the occurrence and development of osteosarcoma by regulating the miR-129-5p/LARP1 axis, which suggests that KCNQ1OT1 might be a new biomarker related to proliferation and drug resistance of osteosarcoma. Here, LARP1 is linked to osteosarcoma.