Introduction: This study investigates the relationship between serum biomarkers and the detection of hepatocellular carcinoma (HCC) in different fisher groups in Bangladesh. The research adopts a descriptive and experimental approach to demonstrate the health risks faced by fishermen, including tobacco consumption, polluted drinking water, and insufficient sunlight exposure. Method: We used serum biomarkers such as vitamin D, alpha-fetoprotein (AFP), creatinine (Cr), and hemoglobin A1C (HbA1c) to evaluate their significance in distinguishing between different categories and sexes. Result: We determined a strong and direct correlation between insufficient vitamin D levels and an increased risk of liver cancer. The combination of AFP, vitamin D, and Cr (AFP+Vit-D+Cr) emerges as a highly predictive tool, enhancing diagnostic accuracy and providing a reliable means of identifying hepatocellular carcinoma. Conclusion: The identified correlation showed the significance of addressing lifestyle factors and promoting nutritional support to mitigate the risk of liver cancer