Tachykinins such as SP (substance P) may be involved in the progression of gastric adenocarcinoma through binding to NK-1 receptor. However, the existence and relationship between SP and gastric cancer progression and differentiation remained unknown. We have studied the NK-1 receptor in human gastric cancer tissue and MKN45 cell line and found SP-containing nerve fibres in human gastric cancer and found that the amounts of SP-positive nerves were related to gastric cancer differentiation. SP could promote proliferation, adhesion, migration and invasion of MKN45 cells in vitro. In addition, the intracellular calcium level of MKN45 cells was elevated after SP stimulation, and administration of CRACs (calcium release-activated calcium channels) inhibitor SKF-96365 could partially abolish these effects induced by SP. These results demonstrated that NK-1 receptor and SP-containing nerves existed in human gastric cancer; SP positive nerves may play an important role in human gastric cancer progression, and calcium is critically significant among SP-induced biological effects.