Members of the let-7 family have been shown to play a critical role in cell differentiation and tumorigenesis. However, potential targets of let-7 are still unclear. In the current study, we used bioinformatic analysis combined with DNA sequence analysis to identify potential let-7 targets. We discovered that dentin matrix protein 1 (DMP1), which is a non-collagenous protein essential in the mineralization of dentin and bone, has a let-7 binding site in its 3'-untranslated region. Furthermore, reporter assays demonstrated that the DMP1 3'-untranslated region can be regulated directly by the members of let-7. Gene expression levels of let-7 and DMP1 were validated by qRT-PCR of dental pulp cells cultured in a mineralizing medium. Our results suggest that DMP1 is regulated post-transcriptionally by let-7 during odontoblast differentiation.