Abstract: In this paper, automatic differentiation is applied to sensitivity analysis in distillation column optimization.Sensitivity analysis was aimed to estimate the influence with the presence of uncertainties in distillation column optimization.The column was modeled in semi-open-equation manner.Automatic differentiation(AD) and implicit function differentiation rule(IFDR) were used to calculate the precise absolute and relative sensitivity coefficients, with no truncation error introduced.The proposed approach was verified in sensitivity analysis of a practical distillation column optimization. Its result was compared with that of the finite difference (FD)method.This approach is not only error-free, but also of general purpose.