Background: Hepatocellular carcinoma (HCC) represents a major worldwide health concern, often diagnosed at advanced stages, resulting in poor prognosis. Timely detection is critical for improving patient outcomes. Serum biomarkers have shown promise in facilitating early HCC diagnosis, but their effectiveness can vary among different demographic groups. Objective: The objective of this extensive investigation was to assess the diagnostic capability of cancer antigen 19.9 (CA19.9), carcinoembryonic antigen (CEA), and alphafetoprotein (AFP) as biomarkers for the early detection of HCC. We aimed to evaluate their performance concerning various demographic factors, such as age, gender, and place of residence. Methods: The investigation was conducted in Bangladesh’s Dhaka at the Ibn Sina Diagnostic and Imaging Center. In a cross-sectional analysis conducted between March 2022 and February 2023, 412 patients were included. Advia XPT was used for data collection, while SPSS version 23 was used for analysis. Age, gender, education level, occupation, and place of residence were among the demographic details that were noted. The amounts of serum biomarkers were assessed, and their usefulness for diagnosis was assessed. Results: Among the 412 patients in the study, the distribution across age groups revealed that the majority (105, 25.5%) were aged 51-55. In terms of gender, 294 (71.4%) were male, while 118 (28.6%) were female. Significant variations in biomarker levels were observed across demographic groups. AFP, CEA, and CA19.9 demonstrated varying sensitivities and specificities within different age groups and gender distributions. Notably, AFP showed promising results, particularly in older age groups, with a sensitivity of 81.7% and specificity of 88.4% in patients aged 51-55. AFP exhibited the highest diagnostic accuracy, followed by CA19.9 and CEA. Conclusions: This study highlights the diagnostic potential of serum biomarkers, especially AFP, in the early detection of HCC. Age-specific variations in biomarker performance suggest the importance of considering demographic factors when assessing their efficacy. These findings offer valuable insights for tailoring early HCC diagnosis strategies, ultimately improving patient outcomes.