The aim of the present study was to evaluate the effects of Bacillus amyloliquefaciens fsznc-06 and Bacillus pumilus fsznc-09 on the expressions of spleen genes in weanling Jintang black goats. Bacillus amyloliquefaciens fsznc-06 (BA-treated group) and Bacillus pumilus fsznc-09 (BP-treated group) were directly fed to goats, and the spleens were harvested for transcriptome analysis. The KEGG pathway analysis showed that the differentially expressed genes (DEGs) in BA-treated vs CON group were mainly involved in digestive system and immune system, while those in BP-treated vs CON group were mainly involved in immune system, and those in BA-treated vs BP-treated group were mainly involved in digestive system. In conclusion, Bacillus amyloliquefaciens fsznc-06 might promote the expressions of genes related to immune system and digestive system, reduce the expressions of disease genes related to digestive system and might promote mutual accommodation of some immune genes in weanling black goat. Bacillus pumilus fsznc-09 might promote the expressions of genes related to immune system and mutual accommodation of some immune genes in weanling black goat. Bacillus amyloliquefaciens fsznc-06 has advantages over Bacillus pumilus fsznc-09 in promoting the expressions of genes related to digestive system and mutual accommodation of some immune genes.