The line loss rate is an important basis to reflect line loss management. Due to the complexity of its theoretical calculation, it has been widely concerned by power workers. Based on the current research status of line loss management at home and abroad and related theoretical calculation methods, a multiple linear regression model based on the K-Means clustering algorithm is proposed to predict the line loss rate of the station area. Firstly, the proposed K-Means clustering algorithm is utilized to cluster and analyze the sample data of the station area. Linear regression prediction models are established to calculate the line loss rate of the station area according to the clustering results. Then, through the comparison and analysis of the predicted line loss rate and the actual line loss rate, much attention is paid on the stations with large errors in line loss estimation. Finally, Finally, based on the sample data of some regions in Guizhou, the accuracy and rapidity of the proposed method are verified, which provides a theoretical basis for line loss management in Guizhou.