RUSC1-AS1 is a novel oncogenic lncRNA in osteosarcoma through the miR-101-3p-Notch1-Ras-ERK pathway, which might be a potential therapeutic target for osteosarcoma. Astaxanthin down-regulates RUSC1-AS1 significantly attenuated the proliferative, epithelial-mesenchymal transition (EMT), growth, lung metastasis, migrative and invasive abilities of MG-63 and Saos-2 cells. The gene discussed is NOTCH1; the disease is osteosarcoma.