Acrylamide has been studied for its carcinogenicity in experimental animals, causing tumors at several organ sites, and has been considered probably carcinogenic to humans as well. Given the small number of epidemiological studies that have been conducted, it is still uncertain whether the consumption of acrylamide is associated with liver cancer. Therefore, we investigated a study to determine the possible relationship between acrylamide intake and the risk of developing liver cancer in the Japanese population. A total of 85,305 participants, from the Japan Public Health Center-based Prospective Study, who provided a validated food-frequency questionnaire were enrolled between 1995 and 1998. During a median of 16.0 years follow-up, 744 new liver cancer cases were identified. Compared to the lowest tertile of acrylamide consumption (<4.8 µg/day), the multivariate hazard ratio (HR) for the highest tertile (≥7.6 µg/day) was 0.79 (95% confidence interval [CI] = 0.65-0.95) for liver cancer using multivariable model 1, adjusted for smoking status, body mass index (BMI), physical activity, medical history, and alcohol consumption; whereas the inverse relationship disappeared after additionally adjusting for coffee consumption in multivariable model 2 with HR of 1.08 (95% CI = 0.87-1.34) for the highest tertile. The effect of dietary acrylamide intake on the risk of liver cancer was not observed in the Japanese population.