Current automation-assisted technologies for screening cervical cancer mainly rely on automated liquid-based cytology slides with proprietary stain. This is not a costefficient approach to be utilized in developing countries. In this article, we propose the first automation-assisted system to screen cervical cancer in manual liquid-based cytology (MLBC) slides with hematoxylin and eosin (H&E) stain, which is inexpensive and more applicable in developing countries. This system consists of three main modules: image acquisition, cell segmentation, and cell classification. First, an autofocusing scheme is proposed to find the global maximum of the focus curve by iteratively comparing image qualities of specific locations. On the autofocused images, the multiway graph cut (GC) is performed globally on the a* channel enhanced image to obtain cytoplasm segmentation. The nuclei, especially abnormal nuclei, are robustly segmented by using GC adaptively and locally. Two concave-based approaches are integrated to split the touching nuclei. To classify the segmented cells, features are selected and preprocessed to improve the sensitivity, and contextual and cytoplasm information are introduced to improve the specificity. Experiments on 26 consecutive image stacks demonstrated that the dynamic autofocusing accuracy was 2.06 lm. On 21 cervical cell images with nonideal imaging condition and pathology, our segmentation method achieved a 93% accuracy for cytoplasm, and a 87.3% F-measure for nuclei, both outperformed state of the art works in terms of accuracy. Additional clinical trials showed that both the sensitivity (88.1%) and the specificity (100%) of our system are satisfyingly high. These results proved the feasibility of automation-assisted cervical cancer screening in MLBC slides with H&E stain, which is highly desirable in community health centers and small hospitals. V C 2013 International Society for Advancement of Cytometry