Background: The Illness Perception Questionnaire-Revised (IPQ-R) has commonly been used to measure illness representations of various diseases. The present study examined whether the original factor structure of the IPQ-R could be confirmed or a new structure could be established on substance dependence among injecting drug users (IDU) in China. Methods: A total of 257 IDU completed the 38-item IPQ-R on substance dependence. Results: Results of confirmatory factor analysis (CFA) showed that the 7-factor structure as proposed by the original IPQ-R reported poor goodness-of-fit statistics. Although removal of 12 items improved the model fit, the goodness-of-fit statistics were still below acceptable standards. Furthermore, factors obtained from the exploratory factor analysis (EFA) of the IPQ-R were not interpretable. Conclusions: The CFA found that the original IPQ-R factor structure fit the data poorly. Factors derived from EFA were also not interpretable. Use of the IPQ-R for assessment of illness representations of substance dependence among IDU in China is cautioned until further validation.