A cotton cultivar, designated DP 121 RF, is disclosed. The invention relates to the seeds of cotton cultivar DP 121 RF, to the plants of cotton DP 121 RF and to methods for producing a cotton plant produced by crossing the cultivar DP 121 RF with itself or another cotton variety. The invention further relates to hybrid cotton seeds and plants produced by crossing the cultivar DP 121 RF with another cotton cultivar.