MSCs promote osteosarcoma cell survival and drug resistance through activation of STAT3. Inhibition of STAT3 prolongs the survival time of tumour-bearing mice by suppressing tumour growth and increasing the sensitivity of tumour cells to doxorubicin. The increased expression of p-STAT3, multidrug resistance protein (MRP), and P-glycoprotein (MDR-1) is associated with high chemotherapy resistance in clinical osteosarcoma samples. Here, STAT3 is linked to osteosarcoma.