In the circulatory system, the microenvironment surrounding cancer cells is complex and involves multiple coupled factors. We selected two core physical factors, shear stress and hydraulic resistance, and constructed a microfluidic device with dual negative inputs to study the trade-off movement behavior of cancer cells when facing coupled factors. We detected significant shear stress escape phenomena in the MDA-MB-231 cell line and qualitatively explained this behavior using a cellular force model. Through the dual validation of substrate anti-cell-adhesion modification and employment of the MCF-7 cell line, we further substantiated the predictability and feasibility of our model. This study provides an explanation for the trade-off underlying the direction-choosing mechanism of cancer cells when facing environmental selection.