Abstract Background Among women at high risk for HIV and other sexually transmitted diseases (STIs), gender and economic issues limit the impact of behavioral prevention strategies. Women in Kazakhstan with dual risks of sex trading and drug use face elevated risk for HIV and STIs and may benefit from an economic empowerment intervention which combines HIV-risk reduction (HIVRR) education with financial skills-building and asset-building to promote reduced reliance on sex trading for income. Methods/design The study employs a two-arm, cluster-randomized controlled trial (c-RCT) design. We will use cluster randomization to assign 350 women in approximately 50 cohorts to a traditional four-session HIV-risk-reduction intervention combined with a six-session financial literacy intervention, enrollment in a 24-session vocational training program and receipt of matched savings (HIVRR+MF); or to the four-session HIV-risk-reduction intervention alone (HIVRR). Repeated behavioral and biological assessments will be conducted at baseline, then at 6, 9, and 15 months post randomization/session 1. Discussion This study responds to an identified need in the academic literature for rigorous testing of structural interventions, including combination microfinance and HIV-prevention interventions. Trial registration ClinicalTrials.gov, ID: NCT02406482. Registered on 30 March 2015.