The major purpose of this study was to investigate the effects of STS (Science-Technology-Society) instruction on a group of Taiwanese female tenth graders' cognitive structure outcomes. This study further examined the role of student scientific epistemological beliefs on such effects. One hundred and one female tenth graders were assigned to either a STS-oriented instruction group or a traditional teaching group and then this study conducted a eight-month research treatment. Students' interview details, analysed through a 'flow map' method, indicated that STS group students performed better in terms of the extent, richness and connection of cognitive structure outcomes than did traditional group students. Further analyses suggested that STS instruction was especially beneficial to students having epistemological views more oriented to constructivist views of science, particularly in the beginning stage of STS instruction. This implies that learners' scientific epistemological beliefs may be an important factor mediating the implementation of STS-oriented instruction.