The infection with hepatitis B virus is the common cause of liver cirrhosis, and portal hypertensionis is one of the main causes of morbidity and mortality in patients with cirrhosis, which has attracted extensive attention for its fatal complications worldwide. By comparing the expression pattern to normal spleen tissues through RNA-Seq technology, we identified a list of protein-coding genes that were expressed differentially between patient and normal samples. Especially the secretory cytokines, including chemokine activity-related genes and immediate early response genes, were significantly upregulated in spleen samples. The results and genes identified in this study revealed the similar expression pattern in human samples to that reported in murine model, which further support the thesis that the spleen could take a harmful role and provide a negative impact in this situation due to inducing chemokine and transcription factor.