Abstract: Microarray (gene chip) technology has broken the old research model and has been used to study the system of graduate macro expression and function of the object. This process is possible through integrated molecular biology, laser chemistry, computer science, and other disciplines related to technology. Gene chip  has a high throughput, high sensitivity, high specificity, and other parallel characteristics. Osteosarcoma is one of the most common malignant bone tumors. In the last 20 to 30 years, the treatment of osteosarcoma has made significant progress.  A number of studies have shown that integrated chemotherapy can improve the survival rate of patients with osteosarcoma from 20%-30% to 60-70%. Therefore, palliative chemotherapy is no longer a passive treatment, but an important way to reduce tumor recurrence rate, improve the quality of life, and prolong survival. However, the resistance of osteosarcoma cells to chemotherapeutic drug is one of important reasons for chemotherapy failure. Drug resistance is a complicated mechanism, which is decided by the integrated features of tumors, such as the reduction in drug uptake, increase in efflux, DNA damage and repair capabilities, potential to improve resistance to apoptosis, cell membrane permeability reduction, and associated changes in enzyme activity. Using technology to study the mechanism of resistance from the gene level of osteosarcoma can quickly get a large number of resistant genes. Further study of the relationship between resistant genes and the discovery of new resistant genes may provide favorable clues. Thus, gene chip technology can be used as an effective method to study the mechanisms of chemotherapy resistance in osteosarcoma. The current paper discusses the gene chip principle, classification, and characteristics of the resistance mechanisms of osteosarcoma, as well as the applications of gene chip technology.