Streptococcus pneumoniae is a major, encapsulated gram-positive pathogen that causes diseases including community-acquired pneumonia, meningitis, and sepsis. This pathogen colonizes the nasopharyngeal epithelia asymptomatically but can often migrate to sterile tissues and cause life-threatening invasive infections (invasive pneumococcal disease: IPD). Although multivalent pneumococcal polysaccharides and conjugate vaccines are available and effective, they also have major shortcomings with respect to the emergence of vaccine-resistant serotypes. Therefore, alternative therapeutic approaches are needed, and the molecular analysis of host-pathogen interactions and their applications to pharmaceutical development and clinical practice has recently received increased attention. In this review, we introduce pneumococcal surface virulence factors involved in pathogenicity and highlight recent advances in understanding regarding host autophagy recognition mechanisms against intracellular S. pneumoniae and pneumococcal evasion from autophagy. This article is protected by copyright. All rights reserved.This article is protected by copyright. All rights reserved.