The paper aims to analyze the cognitive mechanism of luminance contrast and color combination in the in-vehicle information system interface.Based on the perceptual load paradigm, in experiment A, with the experimental materials of 16 color combinations of four luminance contrast levels (6∶1, 9∶1, 12∶1, and 18∶1), the error rates under high, medium, and low loads were analyzed. In experiment B, an EEG research on the basis of experiment A was conducted. Experiment A:Under high and medium loads, the luminance contrast of 18:1 reduced the target search error rate significantly, while yellow on black, yellow on blue, and white on blue were the three color combinations with the lowest search error rate. However, there is no significant effect under low load. Experiment B:The topographic map of the brain area showed that under the 18∶1 luminance contrast and color combination visual stimulation, the brain areas of the occipital lobe, prefrontal lobe and temporal lobe were more activated. Compared with low load, the brain regions of high and medium load were less activated. ERP analysis found that under the 18∶1 luminance contrast and color combination visual stimulation, the peak value and average amplitude of the P100 curve of the O2 electrode were significantly higher than the other three luminance contrast and color combinations. High luminance contrast (18∶1) should be preferred for information elements and interface background in the interface of in-vehicle information system. In terms of color matching, black or blue should be selected as the background color, and yellow or white as the color of information elements such as icon and text.