The water depth condition of navigation channel affected by the operation of cascade hydropower stations could experience a reverse between flood season and dry season, significantly altering the minimum design navigable discharge of the waterway. The minimum design navigable discharge of the waterway downstream of Honghua dam was determined in consideration of the inflow characteristics of the Qianjiang and Liujiang Rivers, the dispatch operation rules of the Datangxia Reservoir, the peak regulation features of the Honghua hydropower station, as well as the impact of Liujiang River waterway project on low water level. Results indicated that the control period for low water level of Liujiang River would undergo significant changes due to the impoundment of Datengxia Reservoir, and the minimum design navigable discharge of waterway had the potential to increase remarkably. The extensive dredging of Liujiang River navigation channel substantially impacted the low water level downstream of Honghua dam, and the daily peak regulation of Honghua hydropower station was significant. Consequently, it is suitable to adopt the discharge with a 98% guarantee rate at Liuzhou hydrological station in the upstream of Honghua dam from June to August as the minimum navigable control discharge for the downstream waterway. The findings provide valuable information for the analysis and computation of the minimum design navigable discharge of waterways affected by cascade hydropower stations.