Objective To realize the high-efficient capture of circulating tumor cells (CTCs) in the blood of tumor patients by analytic modeling and optimization on the herringbone micro-fluidic chip. Methods By simulating the fluid flow within the herringbone chip with Fluent 15.0 and calculating the capture efficiency with MATLAB to understand how geometric parameters (the herringbone groove width, spacing between herringbone grooves, herringbone groove height and channel height), flow rates and flow directions (forward flow, reverse flow) affected the cell-surface contact for capture of the CTCs, the capture efficiency was predicted and then validated by experiments. Results The herringbone micro-fluidic chip could achieve the optimal capture rate when the herringbone groove width, spacing between herringbone grooves, herringbone groove height and channel height were 75, 125, 70 and 30 μm, respectively, at a flow rate of 1 mL/h with forward direction. Conclusions In this study, cell capture in different micro-fluidic chips was simulated by the method of computational fluid dynamics. The statistic model of capture efficiency is established by MATLAB and optimized to quickly screen a group of physical parameters for high-efficient cell capture. These optimized micro-fluid chip parameters are validated by experiment, which can realize the high-efficient capture of CTCs.