Lithography hotspot detection is one of the fundamental steps in physical verification. Due to the increasingly complicated design patterns, early and quick feedback for lithography hotspots is desired to guide design closure in early stages. Machine learning approaches have been successfully applied to hotspot detection while demonstrating a remarkable capability of generalization to unseen hotspot patterns. However, most of the proposed machine learning approaches are not yet able to answer one critical question: how much a hotspot predicted from a trained model can be trusted? In this work, we present Litho-GPA, a lithography hotspot detection framework, with Gaussian Process assurance to provide confidence in each prediction. The framework also incorporates a data selection scheme with a sequence of weak classifiers to sample representative data and eventually reduce the amount of training data and lithography simulations needed. Experimental results demonstrate that our Litho-GPA is able to achieve the state-of-the-art accuracy while obtaining on average 28% reduction in false alarms.