We propose a CMOS image sensor which can capture both whole images at 60 fps and several region-of-interests (ROIs) images at a high-speed frame rate of 2.1 kfps. We have designed a sensor prototype for our newly developed man-machine interface system called “Opto-Navigation”. In the system, LEDs as optical beacons are equipped with portable devices such as mobile phones and digital cameras, and provide a useful guide for visually aided data communication with them. The optical beacons inform their positions at slow frequency around 10 Hz, which define ROIs, and send their ID data with bit rate of 1kbps to the sensor. The sensor can recognize the position of IDs with frame differences of 60-fps images and then obtain the ID data by reading only ROIs at high frame rate. Thus by using the image sensor a user can know what devices can be communicated with and select one of them to send/receive information data. A QVGA image sensor dedicated for the “Opto-Navi” system has been fabricated in a 0.35-μm 2-poly 3-metal standard CMOS technology. The pixel has 7.5 × 7.5 μm2 area with a fill factor of 24.9%.