Vibrio vulnificus, a gram-negative halophilic marine bacterium and opportunistic pathogen, must withstand various environmental changes, especially the simultaneous change of temperature and salinity (SCTS) from $25^{circ}C$/2.5% to $37^{circ}C$/0.9% upon entering the human body. Previous studies have suggested that temperature and salinity may affect the production of metalloprotease VvpE via the LuxS-mediated autoinducer-2 quorum sensing system (AI-2-QSS). However, this hypothesis remains to be verified through coherent experiments. In this study, SCTS stimulated V. vulnificus growth with no increase in total growth levels. The SCTS-mediated prolongation of the stationary growth phase resulted in a significant increase in growth phase-dependent luxS and vvpE transcriptions; however, SCTS did not affect luxS or vvpE transcription levels during the exponential growth phase. SCTS also advanced extracellular VvpE production, which was consistent with vvpE transcription and V. vulnificus growth. SCTS-mediated modulation of vvpE expression was slightly attenuated but still observed in the background of a luxS mutation which seriously repressed vvpE expression. These results indicate that SCTS stimulates luxS and vvpE expression by stimulating V. vulnificus growth; however, the LuxS-mediated AI-2-QSS plays only a minor role, if any, in the SCTS-mediated modulation of vvpE expression.