This paper presents a novel effective method for the optimization of a lead flotation with multiple performance characteristics based on the grey relational analysis (GRA). The lead flotation parameters including potassium amyl xanthate (KAX) as a collector, sodium sulfide (Na2S), and slurry pH were optimized based on multiple performance characteristics. Sixteen experiments have been conducted using GRA to optimize the settings for the lead flotation parameters to generate two quality characteristics (grade and recovery of the concentrate). Analysis of the grey relational grade indicates that parameter significance and the optimal parameter combination for the lead flotation process are identified. The analytical results from two confirmation experiments using the optimal parameters confirm that the above performance characteristics in the lead flotation process can be improved effectively through this approach.