The optimization method was established to investigate the effect of near infrared chemical imaging (NIR-CI) detection parameters on hyperspectral data quality. In order to optimize the detection parameters, chlorpheniramine maleate (CPM) tablets were chosen as examples and the L9(34) orthogonal-test design was adopted to research the effects of spectral resolution, spatial resolution, scan times and scan height. Binary image coupled with statistical measurement was proposed to quantitatively analyze hyperspectral data and determine the content of CPM on the tablet surface. High-performance liquid chromatography (HPLC) was used as reference method for accurate CPM determination. The absolute value of the difference between CPM contents obtained from NIR-CI and HPLC was chosen as index. The result demonstrated that the optimum parameters for acquiring hyperspectral data were: 25 μm×25 μm (spatial resolution), 5340 (scan height, the value of Z, precise focus), 16 cm-1(spectral resolution) and 16 (scan times). The influence of scan height on hyperspectral data was firstly investigated. The optimized parameters could be applied to CPM tablets and other drugs for NIR-CI data acquisition and methodology establishment.