To monitor industrial processes properly, softsensors are widely used to predict significant but difficultto-measure quality variables. However, the prediction performances of traditional data-driven soft-sensors are usually unacceptable once suffering from high-nonlinear, high-dimension and imblance data issues. Therefore, a semi-supervised soft-sensor, which is learned by a just-intime method with structure entropy clustering (SS-JITL-SEC), is proposed aiming to improve prediction performance with a simpler way. Inspired by a divide and conquer strategy, a novel SEC method is proposed to achieve several clusters and then to translate the highly complex and nonlinear modeling problems into simple and linear ones. Moreover, the training dataset is extended through a mixed semi-supervised (SS) labeling approach. Finally, dissimilarity-based just-in-time learning (JITL) works together with the resulting clustering sub-datasets to formulate a local adaptive prediction model. Two datasets from different types of wastewater treatment plants are used to verify the effectiveness of the proposed soft-sensor. The results show that the SS-JITL-SEC soft-sensor can achieve better prediction performance than other standard counterparts, and even for effective process monitoring with the resulted residuals.Impact Statement -Proper processes monitoring of difficult-tomeasure quality-related variables is imperative for safe and stable operation of industrial processes, particularly under the case of suffering from significantly dynamic, highly dimensional behaviors during supervised learning. Data-driven soft-sensors together with adaptive learning and semi-supervised learning are currently the alternatives to achieve this goal. The novelty of