Abstract： Cancer pain is a global health issue.With a deeper understanding of the molecular mechanisms underlying cancer pain,researchers have found that cancer pain is not only a consequence of tumor development but also plays a role in promoting tumor growth.Cancer pain is accompanied by the activation of various"cancer pain signaling molecules"such as calcitonin gene related peptide(CGRP),endothelin B receptor,(ETBR),tropomyosin-receptor kinase A(TrkA),voltage-gated sodium channel 1.3(Nav1.3),Nav1.7,Nav1.9,substance P(SP),neurokinin-1 receptor(NK-1R),transient receptor potential A1(TRPA1)and transient receptor potential vanilloid 1(TRPV1).These molecules can influence the mechanical strength of the extracellular matrix,pH,Ca2+concentration,and reactive oxygen species content in the tumor microenvironment,providing favorable conditions for tumor proliferation,migration,and invasion.Simultaneously,various cells in the tumor microenvi-ronment can enhance the effects of cancer pain signaling molecules by releasing chemical signals and generating mechanical stimulation.This review summarizes the crucial role of cancer pain signaling molecules in remodeling the tumor microenvironment and promoting the malignant progression of tumors.It reveals the interactive mech-anism of tumor-cancer pain-tumor microenvironment-tumor progression,providing important theoretical support and research directions for the effective management of cancer pain and the innovation of tumor treat-ment strategies.