Objectives: Lung cancer is the most frequent malignant tumor. Tumor necrosis factor- (TNF-) is cytokine involved in many way in the pathogenesis of various inflammatory diseases and malignant tumor. Previous studies investigating the role of the TNF- gene polymorphisms in lung cancer patients have generated different results. In the present study, the aim was investigated whether the TNF- -308 and TNF--238 polymorphisms influence on the susceptibility and/or severity of lung cancer in Croatian population. This is the first study in Caucasian population which include this two polymorphisms in all types of lung cancer. Patients and Methods: In this randomised study 230 lung cancer patients was investigated. Non-small cell lung cancers (NSCLC) and small cell lung cancer (SCLC) were included. Control group was 230 appropriate age and sex-matched healthy controls. After DNA isolation from peripheral blood that were genotyped by the polymerase chain reaction/restriction fragment length polymorphism method, results are statistically analysed. Results: There were no significant differences in the genotype and allele frequencies for the TNF--308 and TNF--238 polymorphisms between lung cancer patients and controls. We did not detect any association between the genotypes, different stages of lung cancer and the pathohistological findings, when we observed all the patients. Meanwhile, when the genotypes were compared between stages of lung cancer and non-small cell lung cancer and small cell lung cancer, GG TNF--238 in small cell lung cancer was statistically significantly more frequent (p=0,02), than genotypes GA and AA in extensive disease of small cell lung cancer. In the group of NSCL there was not any differences. Investigating laboratory blood findings in correlation with genotypes frequencies, a significant statistically correlation was found only for high level of neutrophil granulocytes and low total proteins in the peripheral blood and TNF--308 A allele. For these blood parameters in the patients the TNF--308 A allele is risky, whereas -308 G allele is protective. We analysed also genotypes of patients in which lung cancer was the second or third primary malignant tumor. TNF--238 GG genotype was presented in all of them (28) (p=0,000). It mean that G allele TNF--238 has promotive effect for lung cancer development as a second primary tumor. Conclusion: The present study indicates that the TNF--308 and TNF--238 polymorphisms do not influence susceptibility to or severity of lung cancer in Croatian population, when we take into consideration all patients together. Moreover, when we formed NSCLC and SCLC group, G allele TNF--238 take to more severe form of SCLC. As well, G allele TNF--238 had promotive effect for lung cancer when this tumor was the second primary malignant tumor in the same patient.