High-throughput toxicogenomics as an advanced toolbox of Tox21 plays an increasingly important role in facilitating the toxicity assessment of environmental chemicals. However, toxicogenomic dose-response analyses are typically challenged by limited data, which may result in significant uncertainties in parameter and benchmark dose (BMD) estimation. Integrating historical data via prior distribution using a Bayesian method is a useful but not-well-studied strategy. The objective of this study is to evaluate the effectiveness of informative priors in genomic dose-response modeling and BMD estimation. Specifically, we aim to identify plausible informative priors and evaluate their effects on BMD estimates at both gene and pathway levels. A general informative prior and eight time-specific (from 3 h to 29 d) informative priors for seven commonly used continuous dose-response models were derived. Results suggest that the derived informative priors are sensitive to the specific data sets used for elicitation. Real data-based simulations indicate that BMD estimation with the time-specific informative priors can achieve increased or equivalent accuracy, significantly decreased uncertainty, and a slightly enhanced correlation with the points of departure estimated from apical end points than the counterparts with noninformative priors. Overall, our study systematically examined the effects of historical data-based informative priors on BMD estimates, highlighting the benefits of plausible information priors in advancing the practice of toxicogenomics.