Salmonella colonization often establishes carrier status in infected animals, which decreases their performance. Salmonella-carrying pigs shed large amounts of bacteria in their feces, and thus they have a negative economic impact on the swine industry. The MS4A8 gene (membrane-spanning 4-domains A8) was significantly activated, by up to 119-fold, in peripheral blood after Salmonella inoculation of pigs. The present study analyzed the correlation of peripheral blood expression level and a genetic variant of porcine MS4A8 with Salmonella-infection traits. The result indicated that MS4A8 expression levels correlated significantly with Salmonella shedding counts. Both the expression of MS4A8 and fecal shedding counts correlated with leukocytes, lymphocytes, monocytes, segmented neutrophils, and banded neutrophils. A novel single nucleotide polymorphism of porcine MS4A8 (nonsynonymous, Val > Ala) was associated with Salmonella shedding counts and average daily gain (ADG) of body weight. The TT genotype had higher fecal shedding counts, leukocyte counts, and lymphocyte counts than the TC and CC genotypes. The CC genotype had higher level of ADG than the TC and TT genotype (p < 0.05). Those results indicated that MS4A8 is intriguing and could be used as a prospective genetic marker for Salmonella susceptibility.