This paper presents a physics-based engineering approach to estimate the heavy ion induced upset cross section for 6T SRAM cells from layout and technology parameters. The new approach calculates the effects of radiation with junction photocurrent, which is derived based on device physics. The new and simple approach handles the problem by using simple SPICE simulations. At first, the approach uses a standard SPICE program on a typical PC to predict the SPICE-simulated curve of the collected charge vs. its affected distance from the drain-body junction with the derived junction photocurrent. And then, the SPICE-simulated curve is used to calculate the heavy ion induced upset cross section with a simple model, which considers that the SEU cross section of a SRAM cell is more related to a “radius of influence” around a heavy ion strike than to the physical size of a diffusion node in the layout for advanced SRAMs in nano-scale process technologies. The calculated upset cross section based on this method is in good agreement with the test results for 6T SRAM cells processed using 90 nm process technology.