Abstract Background HIV/HCV coinfection is associated with a rapid progression to liver damage. Specifically, the dysregulation of NK cell populations is of special interest, as NK cells have been shown to effectively block HCV replication as well as an anti-fibrogenic activity. The NKp30 receptor has been linked to tumor cell lysis and has a crucial role during viral infections. In the present study, we determine the subpopulations of NK cells and the expression of NKp30 receptor and cytotoxicity molecules in patients with HIV/HCV. Results HIV/HCV coinfected patients present greater liver damage than the HIV control group, using the APRI and FIB-4 indices. NK cells frequency was decreased in the HIV/HCV group compared to the HIV group. CD56brigth cell frequency was increased and CD56dim was decreased in HIV/HCV patients. NKp30 expression was higher in CD56brigth subpopulation and lower in CD56dim subpopulation in the HIV/HCV group. However, the expression of the ζ chain (p < 0.0001), granzyme B, and perforin (p = 0.0474), were significantly decreased in CD56dim NKp30 + cells from HIV/HCV patients. Conclusions The expansion of the highly dysfunctional CD56brigth subpopulation and the low expression of cytotoxicity markers in CD56dim cells reflects an altered activity in NK cells of coinfected patients, which could contribute to the accelerated progression of liver damage.