Background: Dental pulp mesenchymal stem cells' secretome (DPMSCs-sec) possess a variety of regenerative properties as well as therapeutic potential for cancer patients. However, since DPMSCs-sec has been scientifically demonstrated to promote prostate cancer cells, caution is advised. As a result, to ensure the safety of their application, it is crucial to determine whether these pro-carcinogenic criteria affect other cancer types. In this study, we explored the effects of DPMSCs-sec and stimulated DPMSCs-sec on the proliferation, apoptotic potential, and response to the chemotherapeutic drug (Taxotere) of head and neck cancer cells (HNO97). Methods: DPMSCs-sec was prepared. The cytotoxic and proapoptotic effects of DPMSCs-sec on HNO97 cells were evaluated using a cell proliferation assay and Annexin V-PI staining. Results: DPMSCs-sec did not increase proliferation of HNO97 cells, nor increased resistance to Taxotere. On the contrary, it induced apoptosis. Concomitant exposure of HNO97 cells to DPMSCs-sec and Taxotere showed significant increase to its cytotoxic effects. Conclusions: Our in vitro results revealed that DPMSCs-sec was not tumorigenic regarding proliferation, apoptosis, and drug resistance. Further animal studies are required to determine its impacts on further cancer-causing characteristics, such as stemness, migration, adhesion, invasion and metastasis.