Heparin cofactor (HCII) is a member of serine protease inhibitors (SPIs) family of genes which play a fundamental physiological role in different biological processes including hemostasis. Therefore, this study aimed to cloning a partial nucleotide sequence of Nile Tilapia HCII cDNA and examine its expression level in the liver tissue following the intracoelomic injection of benzo-a-pyrene BaP. The cloned nucleotide sequence contained 972 bp representing a 666 bp of the Open Reading Frame (ORF) encodes for 221 amino acids and a stop codon and a 306 bp of the 3′ noncoding region. The amino acids sequence comparison and phylogenetic tree analysis showed a close relationship between tilapia and Pundamilia nyererei serpind1 sequences. Realtime-PCR results showed high expression level (6.2) of Serpind1 mRNA in the liver of the BaP-treated fish compared with the control group suggesting the physiological role of HCII in tilapia. The study proposed the use of tilapia fish as a mammalian hemostasis model depending on the hemostatic genes homology analysis.