Partial least squares (PLS) and linear regression methods are widely utilized for quality-related fault detection in industrial processes. Standard PLS decomposes the process variables into principal and residual parts. However, as the principal part still contains many components unrelated to quality, if these components were not removed it could cause many false alarms. Besides, although these components do not affect product quality, they have a great impact on process safety and information about other faults. Removing and discarding these components will lead to a reduction in the detection rate of faults, unrelated to quality. To overcome the drawbacks of Standard PLS, a novel method, MI-PLS (mutual information PLS), is proposed in this paper. The proposed MI-PLS algorithm utilizes mutual information to divide the process variables into selected and residual components, and then uses singular value decomposition (SVD) to further decompose the selected part into quality-related and quality-unrelated components, subsequently constructing quality-related monitoring statistics. To ensure that there is no information loss and that the proposed MI-PLS can be used in quality-related and quality-unrelated fault detection, a principal component analysis (PCA) model is performed on the residual component to obtain its score matrix, which is combined with the quality-unrelated part to obtain the total quality-unrelated monitoring statistics. Finally, the proposed method is applied on a numerical example and Tennessee Eastman process. The proposed MI-PLS has a lower computational load and more robust performance compared with T-PLS and PCR.