China is experiencing a rapid increase in the number of HIV-infected women. In this study, we describe the development and preliminary evaluation of an intervention tailored for Chinese HIV-infected women and caregivers to improve their self- and family management, with goals of enhancing their physical quality of life (QOL) and decreasing their depressive symptomatology. Forty-one HIV-infected women and their caregivers were recruited from two premier Chinese hospitals from July 2014 through March 2016. Participants were randomized to either the control or intervention arm for the Self- and Family Management Intervention (SAFMI). Each study dyad in the intervention arm received three counseling sessions with a nurse interventionist. At baseline, immediate post-intervention (month 1) and follow-up (month 3), the participants were assessed by a self-reported survey. Generalized Hierarchical Linear Modeling was used to evaluate the efficacy of the intervention. Chinese HIV-infected women in the intervention arm had significantly higher probability of higher physical QOL at month 1 and lower probability of clinically meaningful depressive symptomatology at month 3 compared with women in the control arm. In contrast, the effects of the intervention were less salient for caregivers. This study represents one of the first in China to include family caregivers in HIV management. Feasibility and acceptability were high, in that family members were willing to join the study, learn about HIV, and practice new skills to support the HIV-infected women in their lives. A larger trial is needed to fully evaluate this intervention which shows promising preliminary effects in promoting physical QOL and decreasing depressive symptomatology among Chinese HIV-infected women.