In the electricity market environment, the regional integrated energy system (RIES) can reduce the total operation cost by participating in electricity market transactions. However, the RIES will face the risk of load and electricity price uncertainties, which may make its operation cost higher than expected. This paper proposes a method to optimize the operation cost of the RIES in the electricity market environment considering uncertainty. Firstly, based on the operation cost structure of the RIES in the electricity market environment, the energy flow relationship of the RIES is analyzed, and the operation cost model of the RIES is built. Then, the electricity purchase costs of the RIES in the medium- and long-term electricity markets, the spot electricity market, and the retail electricity market are analyzed. Finally, considering the risk of load and electricity price uncertainties, the operation cost optimization model of the RIES is established based on conditional value-at-risk. Then it is solved to obtain the operation cost optimization strategy of the RIES. Verification results show that the proposed operation cost optimization method can reduce the operation cost of high electricity price scenario by optimizing the energy purchase and distribution strategy, constrain the risk of load and electricity price uncertainties, and help balance the risks and benefits.