Female sex workers (FSWs) who inject drugs have higher risks of HIV infection due to injection drug use and the array of sexual practices employed. This study, therefore, is designed to determine sexual practices of FSWs who inject drug in Osogbo, Nigeria. This study was a cross-sectional descriptive mixed-methods design. Twenty-seven FSWs who inject drug were selected from 11 brothels by snowball sampling and interviewed with a semistructured questionnaire and in-depth interview guide. The mean age of respondents was 26.2 ± 7.5. Many of the respondents were aware of the magnitude of HIV and some were sex workers first before turning to be drug users. Some of the respondents had ever tested for HIV and few had ever been treated for STI more than once. Some respondents were willing to have male clients who do not wear a condom in exchange for accepting more money in return. Many of the respondents reported use of condom, regular talking of herbs, and good personal hygiene as ways of protecting themselves from HIV. Respondents have relatively high numbers of sexual partners. Involving sex workers directly in HIV prevention campaigns will encourage them to look after their health and to access services that could help them.