Type 2C protein phosphatases (PP2C) are monomeric enzymes that require magnesium or manganese ions for their activities. There are seven PP2C genes in Candida albicans. Here, we demonstrate that CaPTC5 encodes a mitochondrial PP2C enzyme. Expression of CaPTC5 transcripts remains constant during the serum-induced hyphal development. Deletion of CaPTC5 does not affect the in vitro filamentation but renders C. albicans cells sensitive to terbinafine and cadmium, and this sensitivity is complemented by the Saccharomyces cerevisiae ScPTC5. Deletion of CaPTC6 does not have any additive effect on, but deletion of CaPTC7 blocks, the terbinafine sensitivity owing to deletion of CaPTC5. In addition, we have shown that deletion of CaPTC6 also renders C. albicans cells sensitive to cadmium, while deletion of CaPTC7 leads to a high cadmium tolerance, and this tolerance is abolished by further deletion of CaPTC5 or CaPTC6. Furthermore, double deletion of CaPTC6 and CaPTC7 renders C. albicans cells more tolerant to azoles, but deletion of CaPTC5 and CaPTC7 slightly increases the azole sensitivity of C. albicans cells. Our results demonstrate that three mitochondrial PP2C genes CaPTC5, CaPTC6 and CaPTC7 interact differentially in the response of C. albicans cells to antifungal drugs and cadmium.