Abstract: The present invention provides a device system structure based on hybrid orientation SOI and channel stress and a preparation method thereof. According to the preparation method provided in the present invention, first, a (100)/(110) global hybrid orientation SOI structure is prepared; then, after epitaxially growing a relaxed silicon-germanium layer and strained silicon layer sequentially on the global hybrid orientation SOI structure, an (110) epitaxial pattern window is formed; then, after epitaxially growing a (110) silicon layer and a non-relaxed silicon-germanium layer at the (110) epitaxial pattern window, a surface of the patterned hybrid orientation SOI structure is planarized; then, an isolation structure for isolating devices is formed; and finally, a P-type high-voltage device structure is prepared in a (110) substrate portion, an N-type high-voltage device structure and/or low voltage device structures are prepared in the (100) substrate portion.