New interventions to reduce HIV and sexually transmitted infections (STI) among female sex workers are introduced into the context of women’s existing prevention beliefs and practices. These indigenous practices affected implementation of our program to introduce female condoms to women in sex-work establishments in southern China. We used ethnographic field observations and in-depth interviews to document common prevention methods women reported using to protect themselves before and during intervention implementation. Individual, sex-work establishment, and other contextual factors, including sources of information and social and economic pressures to use or reject prevention options, shaped their perceptions and selection of these methods and affected adoption of female condoms as an additional tool. Efforts to improve uptake of effective prevention methods among low-income sex workers require attention to the context and spectrum of women’s HIV/STI prevention practices when introducing innovations such as female condoms, microbicides, pre-exposure prophylaxis pills, and others, as they become available.