Lung cancer and melanoma are responsible for almost 25% of cancer deaths in Australia. Despite recent progress with targeted and immuno-therapies, the 5 year survival rate in late stage patients is still<20%. We have previously shown that CHK1 inhibitors are sensitized by subclinical doses of the replication inhibitor hydroxyurea (HU) to kill a high proportion of melanoma and non-small cell lung cancers. Here we report that this drug combination triggers an immunogenic form of apoptosis that can establish a memory immune response to subsequent live tumour challenge. The combination itself has no adverse effects on either T cells proliferation in vitro or an immune response in vivo. The combination also triggers an inflammatory response involving activation of the cGAS-STING pathway and the recruitment of T lymphocytes. Immune profiling of two syngeneic mouse melanoma models shows that the CHK1 inhibitor combination treatment promoted strong T and NK cells infiltration into the tumours although there were also markers of increased immunosuppression. These observations indicate that addition of an immunotherapy to overcome the immunosuppressive effects observed is likely to establish a strong and durable immune response when extrapolated to treating the patients tumour.