Background Children affected by HIV are at risk for poor mental health. We conducted a pilot randomized controlled trial (RCT) of the Family Strengthening Intervention (FSI‐HIV), a family home‐visiting intervention to promote mental health and improve parent–child relationships in families with caregivers living with HIV, hypothesizing that child and family outcomes would be superior to usual care social work services. Methods Eighty two families (N = 170 children, 48.24% female; N = 123 caregivers, 68.29% female) with at least one HIV‐positive caregiver (n = 103, 83.74%) and school‐aged child (ages 7–17) (HIV+ n = 21, 12.35%) were randomized to receive FSI‐HIV or treatment‐as‐usual (TAU). Local research assistants blind to treatment conducted assessments of child mental health, parenting practices, and family functioning at baseline, post‐intervention, and 3‐month follow‐up. Multilevel modeling assessed effects of FSI‐HIV on outcomes across three time points. Trial Registration: NCT01509573, ‘Pilot Feasibility Trial of the Family Strengthening Intervention in Rwanda (FSI‐HIV‐R).' https://clinicaltrials.gov/ct2/show/;NCT01509573?term=Pilot+Feasibility+Trial+of+the+Family+Strengthening+Intervention+in+Rwanda+%28FSI‐HIV‐R%29&rank=1. Results At 3‐month follow‐up, children in FSI‐HIV showed fewer symptoms of depression compared to TAU by both self‐report (β = −.246; p = .009) and parent report (β = −.174; p = .035) but there were no significant differences by group on conduct problems, functional impairment, family connectedness, or parenting. Conclusions Family‐based prevention has promise for reducing depression symptoms in children affected by HIV. Future trials should examine the effects of FSI‐HIV over time in trials powered to examine treatment mediators.