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Abstract Background CC-type glutaredoxins (GRXs) are plant-specific glutaredoxin, play regulatory roles in response of biotic and abiotic stress. However, it is not clear whether the CC-type GRXs are involve in drought response in cassava (Manihot esculenta), an important tropical tuber root crop. Results Herein, genome-wide analysis identified 18 CC-type GRXs in the cassava genome, of which six (namely MeGRXC3, C4, C7, C14, C15, and C18) were induced by drought stress in leaves of two cassava cultivars Argentina 7 (Arg7) and South China 124 (SC124). Exogenous abscisic acid (ABA) application induced the expression of all the six CC-type GRXs in leaves of both Arg7 and SC124 plants. Overexpression of MeGRXC15 in Arabidopsis (Col-0) increases tolerance of ABA on the sealed agar plates, but results in drought hypersensitivity in soil-grown plants. The results of microarray assays show that MeGRXC15 overexpression affected the expression of a set of transcription factors which involve in stress response, ABA, and JA/ET signalling pathway. The results of protein interaction analysis show that MeGRXC15 can interact with TGA5 from Arabidopsis and MeTGA074 from cassava. Conclusions CC-type glutaredoxins play regulatory roles in cassava response to drought possibly through ABA signalling pathway.