A particle filtering algorithm for base calling in the Illumina’s sequencing-by-synthesis platform. ParticleCall is developed by relying on an HMM representation of the sequencing process. Experimental results demonstrate that the ParticleCall base calling algorithm is more accurate than Bustard, Rolexa, and naiveBayesCall. It is as accurate as BayesCall while being significantly faster. Quality score analysis of the reads indicates that ParticleCall has better discrimination ability than BayesCall, naiveBayesCall and Bustard.