AbstractObjectiveCircular RNA‐mitochondrial tRNA translation optimization 1 (circ‐MTO1) not only involves in bioprocess of various cancers, but also regulates osteosarcoma progression by regulating microRNA‐630 (miR‐630). However, the clinical role of circ‐MTO1 and miR‐630 in osteosarcoma is still obscure. This study aimed to assess the correlation of circ‐MTO1 and miR‐630 with disease features and prognosis and to explore their association with each other in osteosarcoma patients.MethodsForty‐four osteosarcoma patients who received neoadjuvant chemotherapy to surgical resection were analyzed in this retrospective study. Then, circ‐MTO1 and miR‐630 expressions were evaluated in tumor and adjacent non‐tumor specimens by reverse transcription quantitative polymerase chain reaction.ResultsCirc‐MTO1 was lower in tumor than in non‐tumor tissues (p<0.001); meanwhile, its elevated tumor expression was correlated with less advanced Enneking stage (p=0.049), good neoadjuvant chemotherapy response (p=0.029), and longer disease‐free survival (DFS) (p=0.047). However, no association was found between circ‐MTO1 and overall survival (OS) (p=0.122). Additionally, miR‐630 in tumor was higher than in non‐tumor tissues (p<0.001), while its raised tumor expression was associated with pathological fracture occurrence (p=0.003), advanced Enneking stage (p=0.036), poor neoadjuvant chemotherapy response (p=0.035), and shorter DFS (p=0.011). However, no association was found between miR‐630 and OS (p=0.066). In addition, tumor circ‐MTO1 was negatively associated with miR‐630 (r=−0.323, p=0.032).ConclusionCirc‐MTO1 and miR‐630 expressions are inter‐correlated and dysregulated in osteosarcoma patients. Besides, they associate with Enneking stage and/or pathological fracture, as well as neoadjuvant treatment response and accumulating DFS in these patients.