Aim To investigate the effect of transient receptor potential vanilloid subtype 1 (TRPV1) on the expression of Ca²＋-dependent transcriptional regulator and the proliferation of rat vascular smooth muscle cell (RVSMC). Methods RVSMCs were cultured in vitro, and TRPV1-specific agonist capsaicin (CAP) or inhibitor capsazepine (CPZ) was used to promote or inhibit the expression of TRPV1. TRPV1 expression was detected by immunocytochemical staining technique. Cell proliferation activity was detected by methyl thiazolyl tetrazolium method. Proliferating cell nuclear antigen (PCNA) protein expression was detected by Western blot. Western blot and quantitative real-time PCR were used to detect the protein expression and mRNA level of Ca²＋-dependent transcriptional regulator such as nuclear factor of activated T cell c1 (NFATc1), calsenilin (CSEN) and myocyte enhancer factor 2C (MEF2C). Results Immunocytochemical staining showed that TRPV1 was mainly expressed in the membrane and cytoplasm of RVSMC, and CAP or CPZ could activate or inhibit the expression of TRPV1. Compared with the control group, CAP could significantly stimulate the proliferation activity of RVSMCs and up-regulate the expression of PCNA protein (P＜0.01). Meanwhile, the protein and mRNA levels of NFATc1 and MEF2C were significantly up-regulated (P＜0.01); The protein expression of CSEN was significantly increased (P＜0.01), and there was no significant change in CSEN mRNA level (P＞0.05). After CPZ treatment, compared with the control group, the proliferation activity of RVSMC and the expression of PCNA protein were decreased (P＜0.01), the protein and mRNA levels of NFATc1 and MEF2C were significantly down-regulated (P＜0.01); The protein expression of CSEN was significantly decreased (P＜0.01), and there was no significant change in CSEN mRNA level (P＞0.05). Conclusion TRPV1 may be involved in promoting RVSMC proliferation by up-regulating the expression of Ca²＋-dependent transcriptional regulator.