Background: Tumor necrosis factor-alpha (TNF-α) is a key proinflammatory cytokine implicated in the development of chronic pancreatitis (CP). Several researchers have looked at the link between the TNF-α-308 polymorphism and CP, however the findings are still controversial. Hence the present study was undertaken to assess the single nucleotide polymorphisms with the expression of TNF-α in CP patients. Materials and Methods: In this prospective study, a total of 54 radiologically confirmed, CP patients and 101 healthy controls were studied for polymorphic analysis of TNF-α in the Department of Surgical Gastroenterology SKIMS over a period of two years from April 2014 to April 2016. Results: The mean age of patients was 35 years with female predominance (55.56%). Majority (50) of patients was having tropical pancreatitis and only 4 had history of alcohol intake. There was no statistically significant relationship between frequencies of mutant TNF-α (308) A allele and the risk of CP in our population. No clinical variable showed significant association with TNF-α (-308) AA genotype. TNF-α expression in serum was significantly more in CP patients (82.035±16.97) than in healthy controls (22.382±63.676), (p<0.0001). We couldn’t find any association with TNF-α expression and clinical variables like age, sex, smoking, alcohol, and diabetes. Also, there was no significant association of TNF α expression in relation to genotype as well. Conclusion: In conclusion, the current study focuses on the significance of TNF-α levels in CP and identifies it as one of the indicators in the disease's genesis.