pR (ST98) is a chimeric plasmid isolated from Salmonella enterica serovar typhi (S. typhi) and mediates both drug-resistance and virulence of S. typhi. Autophagy has been recently reported as an important component of the innate immune response against intracellular pathogen. In this study, we investigated the effect of pR (ST98) on cellular autophagy, apoptosis and bacterial survival in infected fibroblasts. S. typhi strain ST 8 carrying pR (ST98) , Salmonella typhimurium strain SR-11 carrying a 100 Kb virulent plasmid, and avirulent S. typhi strain ST(10) without plasmid were tested in this experiment. Results showed that embryonic fibroblasts infected with ST(8) containing pR (ST98) had decreased autophagy accompanied by increased bacterial survival and apoptosis. Further study showed that autophagy inducer rapamycin reversed pR (ST98) -mediated inhibition of autophagy and reduced apoptosis in infected fibroblasts. Our data indicate that pR (ST98) can inhibit autophagy, thus facilitating S. typhi survival and promoting apoptosis of host cells. This study contributes to understanding the underlying mechanism of pR (ST98) -mediated virulence in S. typhi.