Cluster of differentiation 4 (CD4) is an important molecule in the immune system of animals, which participates in the processes of T-lymphocyte differentiation, maturation, immune response and signal transduction. During this study, we adopted the direct sequencing of PCR products and time-of-flight mass spectrometry methods for the detection of single nucleotide polymorphisms (SNPs) in 382 Yorkshire pigs. The linkage disequilibrium of CD4 gene polymorphisms and their genetic effects on blood routine indexes were also analyzed. The results showed that SNP was screened in intron 1, intron 6 and exon 10, respectively, of the porcine CD4 gene, and each SNP locus was detected in Yorkshire pigs, which had three genotypes with moderate polymorphism. The three SNPs were in strong linkage disequilibrium (r2>0.8), and constituted only two major haplotypes, AGT and CAC (both frequencies accounted for about 97%). The association analysis showed that CD4 gene polymorphisms were significantly correlated with white blood cell, lymphocyte and monocyte count in Yorkshire pigs (P less than 0.05). The white blood cell count and monocyte count in individual animals with CAC/CAC diplotype were significantly higher than those with AGT/CAC and AGT/AGT diplotypes (P less than 0.05). The lymphocyte count in animals with CAC/CAC diplotype were significantly higher than those with the AGT/AGT diplotype (P less than 0.05). This study indicates that CD4 gene is significantly associated with partial blood routine indexes in pigs, and it can be considered as a candidate gene for the study of porcine disease resistance.