Despite several initiatives to subside the global malaria burden, the spread of artemisinin-resistant parasites poses a big threat to malaria elimination. Mutations inPfKelch13 are predictive of ART resistance, whose underpinning molecular mechanism remains obscure. Recently, endocytosis and stress response pathways such as the ubiquitin-proteasome machinery have been linked to artemisinin resistance. WithPlasmodium, however, ambiguity persists regarding a role in ART resistance for another cellular stress defence mechanism called autophagy. Therefore, we investigated whether, in the absence of ART treatment, basal autophagy is augmented inPfK13-R539T mutant ART-resistant parasites and analyzed whetherPfK13-R539T endowed mutant parasites with an ability to utilize autophagy as a pro-survival strategy. We report that in the absence of any ART treatment,PfK13-R539T mutant parasites exhibit increased basal autophagy compared toPfK13-WT parasites and respond aggressively through changes in autophagic flux. A clear cytoprotective role of autophagy in parasite resistance mechanism is evident by the observation that a suppression of PI3-Kinase (PI3K) activity (a master autophagy regulator) rendered difficulty in the survival ofPfK13-R539T ART-resistant parasites. In conclusion, we now show that higher PI3P levels reported for mutantPfKelch13 backgrounds led to increased basal autophagy that acts as a pro-survival response to ART treatment. Our results highlightPfPI3K as a druggable target with the potential to re-sensitize ART-resistant parasites and identify autophagy as a pro-survival function that modulates ART-resistant parasite growth.