Streptococcal toxic shock syndrome (STSS) is a rapidly progressing, life-threatening, systemic reaction to invasive infection caused by streptococci, which is characterized by a cytokine storm in the host. Although the majority of clinical STSS cases are triggered by the superantigens (SAgs), a few STSS cases are not associated with SAgs and the related mechanisms are considered to be complicated. Here, we review the recent research progress on the mechanism of SAgs-independent STSS, including the activation of inflammatory signaling pathways in host triggered by Streptococcus,the activation of inflammatosomes and pyroptosis, the pro-inflammatory cytokines and cytokine storm. We also summarize cell and animal models usually used in STSS research. This review is useful for a better understanding of STSS and provides a theoretical foundation for the research of STSS mechanism.