Introduction: Cancer patients are disproportionately at high risk of developing infections, with a risk of infection about 10 times than that of non cancer patients. Extended Spectrum β-Lactamases (ESBLs) enzyme producing gram-neg. bacteria have been marked as one of the "serious" threat by the center for disease control. This enzyme has the ability to hydrolyze the β-lactam antibiotics and posses a major threat for the immunocompromised and cancer patients. Hence, understanding its prevalence at the grammatical level is important to decide upon the type of drugs to be prescribed. Aim: To study the prevalence of ESBL genes among the gram-neg. bacteria (GNB) isolated from cancer patients. Materials and Methods: The present study was a hospital-based cross sectional study carried out in Microbiol. Division, Malabar Cancer Center, Thalassery, Kerala, India from Jan. 2021 to March 2021. Microbiol. identification of the causative agents was done by staining, culturing and biochem. methods. Screening of the isolates for ESBL was done using Double Disc Synergy Test (DDST). Antibiotic susceptibility testing was carried out using modified Kirby-Bauer disk diffusion method. The ESBL producers were genotypically confirmed through Polymerase Chain Reaction (PCR) and typed accordingly. The data were given as average with standard deviation and analyzed using Microsoft Excel. Results: Out of 1,310 specimens 366 (27.9%) were culture pos. Among the GNB, Escherichia coli (50%) followed by Klebsiella pneumoniae (46.07%), Proteus (1.96%) and Enterobacter cloacae (0.98%) were the predominant isolates. Most of these ESBL producers (Escherichia coli, Klebsiella pneumoniae) were multi drug resistant. However, significant isolates of Escherichia coli (98.03%), Klebsiella pneumoniae (36.1%), Proteus, (50%) and Enterobacter cloacae (100%) were sensitive to immunocompromised. Among 102 ESBL producers, prevalence of blaTEM (67.64%) was highest followed by blaCTX-M (10.78%), blaSHV (14.70%) and blaOXA (18.62%). All of the ESBL producers tested showed the presence of one of four β-lactamase encoding genes by PCR. One of the isolate Proteus mirabilis found to be ESBL producer as confirmed by phenotypic methods but lacked ESBL genes. Conclusion: Higher prevalence of ESBL producing strains warrants stringent measures to tackle the spread of Multi Drug Resistant (MDR) strains. Carbapenems can be considered as the drug of choice against ESBL producers. Highly prevalent blaTEM gene could be considered as potential therapeutical and diagnostic target against the ESBL producing GNBs.