The tumor suppressor protein, p53, plays a major role in cellular responses to stress and DNA damage in animals; despite its critical function, p53 homologs have not been identified in any algal or plant lineage. This study employs a functional and evolutionary approach to test for a p53 functional equivalent in green algae. Specifically, the study: (i) investigated the effect of two synthetic compounds known to interfere with p53 activity; (ii) searched for sequences with similarity to known p53-induced genes; and (iii) analyzed the expression pattern of one such sequence. The findings reported here suggest that a p53 functional equivalent is present and mediates cellular responses to stress in green algae.