Novel virus Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is highly infectious, which often causes severe acute and long-term illness, resulting in an increased rate of mortality and morbidity. Despite human cells being equipped with an antiviral innate immune system, SARS-CoV-2 quickly spread worldwide. A number of Pattern-Recognition Receptors (PRRs) are employed by cells to detect coronavirus infection, and timely interferon responses is immensely effective against SARS-CoV-2. However, the virus is also able to disarm the cell, attacking interferon-associated signaling pathways on multiple levels. Here we systematically analyze the complicated interactions between SARS-CoV-2 proteins and the host interferon signaling system, highlighting the role of cytosolic events in COVID-19 pathogenesis, and summarize a few antiviral pharmaceutic candidates that are potentially able to reduce morbidity and mortality of COVID-19.