Introduction: Irinotecan being anti-neoplastic agent belongs to BCS class II drug with low solubility and permeability that undergoes first-pass metabolism, leading to reduced bioavailability of 9%. Aim: The main objective of this study is to develop irinotecan supersaturble-self nano emulsifying drug delivery system (SSNEDDS) for enhancing solubility and oral bioavailability. Methodology: An oil, surfactant and co-surfactant (canola oil __ampersandsignndash; caproic acid __ampersandsignndash; propylene glycol) are chosen based on the maximum solubility of irinotecan and ratios optimised by constructing pseudo ternary phase diagram and evaluated. The best formulation was chosen for screening of precipitation inhibitor (PI), and based on in-vitro release studies best S-SNEDDS is finalised. Final optimised formulation was characterized for FTIR, particle size, zeta potential, SEM and stability studies. Results: From evaluation studies of irinotecan, formulation F12 displayed maximum drug content(99%), maximum entrapment efficiency(99%) and maximum drug release of 99.96% in 60 min, hence chosen for screening precipitation inhibitor(PI).The F12 containing 2% HPMC AS as PI was found to show high release profile. The particle size for the optimized formulation of S SNEDDS (F12) was found to be 128.23nm with PDI 0.137 and the zeta potential value of -23.45 mV. The FTIR and SEM studies did not indicate any drug excipient interaction and confirm nanosized particles that are stable. Conclusion: Hence the results reveal that, application of S-SNEDDS formulation technique for irinotecan increased solubility and oral bioavailability.