Sunflower (Helianthus annuus L.) is rich source of essential amino acids, omega-6, and linoleic acid, but cadmium (Cd2+) accumulation is hazardous. The higher accumulation of Cd2+ is facilitated by metal tolerance proteins (HaMTPs) in cell membrane of root hairs, and it was hypothyzed that higher expression of a specific antiporter will resist Cd2+ accumulation. We reterived 16 HaMTPs from sunflower genome under Cd2+ stress, and 5% moringa seed extract (MSE). Phylogenetic analysis revealed that HaMTPs were clustered into 7 groups, classified into 5 sub-families, and are true members of cation diffusion facilitators (CDFs) proteins. HaMTP12 have highest 12 introns, HaMTP1 have 11, HaMTP2 have 9, HaMTP9, -10, and -13 have 6, HaMTP11, -12, -14 and -16 have 5, while all 5 members of “E” subfamily have no any intron. RNA-seq and heatmap analysis revealed differential expression of all HaMTPs in selected tissues. Integrative application of 5% MSE increased rate of photosynthesis and ~25% yield by upregulating expression of HaMTP10 under Cd2+ stress, confirmed by qRT-PCR. Expression pattern and presence of stress responsive TC-rich, abscisic acid responsive elements (ABRE), and P-box cis-ele- ments indicated stimulation of HaMTPs under MSE and Cd2+ responsiveness. HaMTP10 protein is a member of Mn-CDF subfamily and an antiporter of Cd2+ revealed by gene ontology and transmembrane topology analysis. In conclusion, integrative application of MSE and/or stable overexpression of HaMTP10 provide precise tools to mitigate Cd2+ accumulation in sunflower.