3D froth information is a significant indicator of working condition recognition in froth flotation. To extract it accurately, the first and key step is camera calibration. Although there have been many camera calibration methods proposed in these years, they cannot handle well for binocular camera calibration in froth flotation. The main reason is that there is an open environment without support surface or special geometric shapes for camera calibration in froth flotation. Therefore, we propose a novel binocular camera calibration method based on key frame sequences and weighted normalized tilt difference. First, we extract a high-quality frame sequence by filtering out incomplete and out-of-focus images from the froth video. Then, we propose a method to measure the tilt degree of the planar plate and extract the key frame sequences of the planar plate based on the tilt difference. After that, we calculate the camera parameters by weighted normalized tilt difference under various poses. The proposed binocular camera calibration method uses the froth video to obtain accurate and robust camera parameters, and does not require auxiliary equipment. Experiments have demonstrated the effectiveness and flexibility of the proposed method in froth flotation.