The plate-fin heat exchanger is one of the most important components of helium liquefaction system as it recovers cold energy from helium gas in the cold box. Because of larger heat transfer surface area and compact geometrical configuration, plate-fin heat exchangers are widely used. The design of heat exchanger using helium as a cryogenic fluid needs high thermodynamic performance with minimum pressure drop which particularly requires the optimization of dimensional array and its geometrical configurations. In this regard, a parametric investigation was performed to compute the effective geometrical parameters and its effect on thermodynamic (effectiveness and log-mean temperature difference) performance has been discussed in detail. The present study aims to design optimization and thermodynamic performance evaluation of plate-fin type heat exchangers used in helium liquefaction systems. The developed helium liquefaction model has been simulated for the most critical liquefier with and without liquid nitrogen precooling, mixed mode, and refrigeration mode. Each component of the liquefaction model has been technically and thermodynamically analyzed and, in particular, four plate-fin heat exchangers have been considered and designed accurately using Aspen EDR®. Initially, the sensitivity analysis was carried out to characterize the most significant geometrical parameters (fin thickness, height, number and arrangement of layers, frequency, and fin type) and their effect on thermodynamic performance and pressure drop. After that, the artificial intelligence model was used to determine the optimal range of such geometrical variables in which the heat exchanger has maximum effectiveness and log mean temperature difference. Finally, the operating conditions obtained from cycle modeling and optimized geometrical datasets have been applied in commercial simulation software Aspen EDR® for plate-fin heat exchangers design. Finally, a comparative thermodynamic analysis has been carried out to determine the performance of all the designed heat exchangers operating at four different modes (boundary conditions).