Abstract: To explore the best cultivation techniques for flue-cured tobacco variety Yunyan 121 in tobacco area of Bijie City, Guizhou Province, effects of fertilization amount, planting density, and remained leaves number on agronomic traits, economic traits, chemical composition, and sensory quality of Yunyan 121 were studied by using quadratic saturation D-optimal design．Rresults showed that fertilizer amount and planting density significantly influenced agronomic traits．When nitrogen amount was 119.85 kg/hm² and planting density was 15000 plants/hm², Yunyan 121 exhibited the best comprehensive agronomic performance．Planting density and remained leaves number had a great influence on economic traits．When nitrogen amount was 103.65 kg/hm², density was 15000 plants/hm², and per plant remained leaves number was 16, Yunyan 121 exhibited the best economic traits．Planting density affected chemical quality relatively large．When nitrogen amount of 91.05 kg/hm², planting density of 15000 plants/hm², and per plant remained leaves number was 22, Yunyan 121 exhibited the best chemical quality performance．Planting density had a relatively large impact on sensory quality．When nitrogen amount of 87.75 kg/hm², planting density of 17610 plants/hm², and per plant remained leaves number was 19, Yunyan 121 exhibited the best sensory quality．Comprehensive evaluation showed that Yunyan 121 exhibited the best comprehensive performance when nitrogen amountwas 88.80 kg/hm², planting density was 16860 plants/hm², and per plant remained leaves number was 17．It was suggested that Yunyan 121 should be further demonstrated and promotion in production．