A large number of cancer patients suffer from pain. Growing evidence suggested that pain might be a serious risk factor for cancer patients. The shared modulators and modulation pathways between neural system and tumor cells, such as various neurotransmitters and neurogenic cytokines, provide essential basis for the effect of pain on tumor. In this article, we reviewed some possible mechanism of this process from two aspects: the systematic regulation of central nervous system on endocrine and immunity, and the regional regulation of peripheral nerves on tumor cells. The aim of this review is to provide more innovative knowledge about pain and cancer and to emphasize the importance of anti-pain in the therapy of cancer.