Medical advances contribute to raise life expectancy of people living with HIV/AIDS (PLHIV). However, they still face challenges related to the disease, thus, quality of life (QOL) became a priority on the field. The self-regulatory model (SRM) guided this study. Illness perceptions (IP) are the beliefs, cognitions, representations of a disease, impacting PLHIV coping strategies and QOL. Tenacious goal pursuit (TGP) is the pursuit of goals with determination, flexible goal adjustment (FGA) is doing it with flexibility, disengaging if necessary, they can both be considered as coping strategies. This study aims to measure the impact of HIV Perception in the QOL of PLHIV mediated by the TGP and FGA. Data was collected from 196 PLHIV with the WHOQOL-HIV Bref, the Brief-IPQ and the FGA and TGP scales. Structural equation model provided a good fit consistent with the theoretical SRM. IP, TGP and FGA had direct effects on the QOL of PLHIV. IP had also an indirect effect (partially mediated by TGP/FGA), suggesting that TGP/FGA reduce the impact of a threatening IP in the QOL. Goal oriented interventions should focus in the HIV perception of PLHIV to ameliorate their QOL.