In order to assess the effect of lindane exposure on gene expression in tilapia (Oreochromis niloticus), twenty male fish were individually weighted and injected intraperitoneally with a single dose of lindane (19.09 mg/kg bw) using corn oil as a carrier vehicle, while a second group of twenty male fish (controls) was only injected with the carrier vehicle. Groups of four fish each were then sacrificed at 3, 6, 12, 18 and 24h after treatment application and total RNA was extracted from liver tissue. The differential display (DD) technique was then used to identify differentially expressed cDNA fragments between treatment and control fish. A total of fifty cDNA fragments were isolated and sequenced, from which only four showed homology with genes previously described in other fish species, namely the immunoglobulin heavy chain (IgH), coagulation factor V (FV), casein kinase 2 alpha (CK2a), and the receptor protein-tyrosine-like phosphatase (RPT-LP). The expression of such genes was confirmed using quantitative real time-polymerase chain reaction (QRT-PCR). Results showed that lindane exposure triggered the differential expression of these genes during the first 6, 18 and 24h subsequent to treatment application, suggesting that lindane exposure can trigger a rapid immune system response in tilapias.