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The discharge of rivers and the subsequent dispersion of their plumes play a pivotal role in the biogeochemical cycling of the Arctic Ocean. Based on the data collected during annual transects conducted in the autumn period (September-October) from 2015-2020, this study explores the effect of River Lena plume dispersion on the seasonal and interannual changes in the hydrophysical and biogeochemical structure of the southeastern Laptev Sea. The temperature-salinity relationship (T-S), Redfield ratio and multiparameter cluster analysis were used to investigate variations in the water mass structure along the transect. The results revealed that the plume’s interannual and seasonal spreading patterns play a crucial role in regulating the local physical, biogeochemical, and biological processes in the southern Laptev Sea. During September-October, the hydrochemical water mass structure along the transects shifted from highly stratified to unstratified as the plume’s mixing intensity increased. Anomalous hydrochemical distributions were observed due to coastal upwelling, which was primarily characterized by high total alkalinity and nitrate levels, and low organic phosphorus, nitrite, and ammonia levels in the seawater. Wind and cold weather conditions drive deep vertical mixing of seawater, causing the resuspension of bottom sediment and the subsequent enrichment of bottom water by nutrients. Multi-parameter cluster analysis is used to describe the details of water mass structures in the highly dynamic southern Laptev Sea, with water mass structures typically undergoing significant changes within two weeks between September and October. The migration and transformation of water masses throughout the seasons are influenced by the volume of river discharge, fall-winter cooling, and atmospheric circulation patterns. Furthermore, the general atmospheric circulation is confirmed to be the primary cause of the interannual variation in the spread of the Lena River plume over the southeast Laptev Sea.