BackgroundMost people who inject drugs (PWID) in Iran have not undergone recent HIV testing. While PWID face barriers when seeking HIV testing at health facilities, HIV self-testing (HIVST) could be a promising approach to improve HIV testing uptake. We examined the awareness and willingness to use HIVST among PWID in Iran. We also identified participants’ characteristics associated with a higher willingness to use HIVST.MethodsPWID were recruited in 11 cities using a respondent-driven sampling method. Willingness to use HIVST was defined as a binary variable (very low/low willingness vs. high/very high willingness). We performed multivariable modified Poisson regression to examine associated factors and report adjusted prevalence ratios (aPR) and 95% confidence intervals (CI).ResultsOf 2,252 PWID, 362 (16.2%; 95% CI 14.7, 17.8) had ever heard of HIVST; however, 1,658 (73.6%; 95% CI 71.7, 75.4) reported high/very high willingness to use HIVST. Willingness to use HIVST was higher among PWID who reported having a high/moderate HIV risk perception (aPR 1.22; 95% CI 1.09, 1.37), ever experiencing homelessness (aPR 1.15; 95% CI 1.03, 1.28), > 10 years of injecting history (aPR 1.16; 95% CI 1.00, 1.34), and high injection frequency in the last three months (aPR 1.18; 95% CI 1.05, 1.32).ConclusionMost PWID in Iran, particularly those experiencing homelessness, have a longer injecting history, engage in more frequent injection practices, and possess a heightened perception of HIV risk would be willing to adopt HIVST. Enhancing HIVST awareness through increased access to HIVST and health education programs are needed. Additionally, conducting implementation science studies to effectively design and run HIVST programs in Iran can also increase PWID’s access to HIV testing.